Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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signal transducer and activator of transcription 3(STAT3) signal transducer and activator of transcription 3(STAT3) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q21.31,
ENSEMBL_GENE_ID ENSG00000168610,
GENERIF_SUMMARY dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma, Modulation of signal transducer and activator of transcription 3 activities by p53 tumor suppressor in breast cancer cells., Cytokine signaling, actdivated by fiboblst growth factor 3 and adapter protein SH-B, Stat1 and Stat3 may support cell growth in part via c-myc gene activation in primary erythroleukemia cells., inhibits gamma-globin gene expression in erythroid cells., Breast Carcinoma cell growth could be inhibited by dominant-negative versions of STAT3., STAT3 isoforms are differentially expressed and phosphorylated during progression of granulocytic differentiation., The C-terminal domain of Stat3 negatively regulates its receptor binding activity only in the absence of the first alpha-helix of the coiled-coil domain, which leads to a hypothesis of intramolecular interaction., The transforming capacity of constitutively activated STAT3 and STAT5 mutants strongly supports their fundamental role in the process of malignant transformation in hematopoietic cells, IL-6-inducible expression of the hAGT promoter is mediated by physical association of the COOH terminus of STAT3 with p300/CBP, the recruitment of which targets histone acetylation and results in chromatin remodeling., STAT5b-RARalpha and other APL fusion proteins may contribute to leukemogenesis by interaction with the STAT3 oncogene pathway., Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells, Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells., Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis, Stat3 activity is significantly increased in both prostate cancer and adjacent normal prostate tissue; activation may be an early event in prostatic epithelial carcinogenesis, Stat3 and GRP58 were observed to be coassociated with cytoplasmic membranes, activated in human ovaarian carcinoma; co-expressed with oncostatin M and its receptor, Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma., activation by type I interferons is dependent on specific tyrosines located in the cytoplasmic domain of interferon receptor chain 2c, STAT3 is activated by HGF/HGFR and has a role in fetal organogenesis and placental tissue, constitutive STAT3 activation contributes to tumor growth in SCCHN, independent of the EGFR autocrine axis., Data show that IL-6/raft/STAT3 signaling is a chaperoned pathway that involves caveolin-1 and HSP90 as accessory proteins and suggest a mechanism for the preservation of this signaling during fever., The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through its dephosphorylation., PKC delta associates with IL6ST via Stat3 and enhances Stat3-gp130 interaction, Platelet signaling pathways activated by thrombopoietin may affect mitochondrial transcription via activation of mitochondrial STAT3, findings suggest that activated STAT3 signaling directly contributes to malignant progression of primary effusion lymphoma by preventing apoptosis, acting through the prosurvival protein survivin, selectively activated in immature dendritic cells by expression of HIV nef, Schwannomin and HRS inhibit Stat3 activation in schwannoma cells., ablation of Stat3 function converts EGF from a growth/survival factor for RA synoviocytes to a death factor, Inhibition suppresses proliferation and induces apoptosis in glioblastoma multiforme cells, Dysregulated STAT3 activity by PML/RAR alpha may participate in the pathogenesis of APL., Kaposi sarcoma-associated viral cyclin K overrides cell growth inhibition mediated by oncostatin M through inhibition of this protein., Stat3 directly regulates VEGF expression and hence angiogenesis, growth, and metastasis of human pancreatic cancer, expression and DNA-binding activity of this protein in alcoholic cirrhosis compared to normal liver and primary biliary cirrhosis in humans, identification of tip60 as a co-repressor for STAT3, inhibition by differentiation-inducing factor-1 is involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway, This protein is activated by leptin which activates the FAAH promoter in T cells., Ataxia telangiectasia mutated proteins, MAPKs, and RSK2 are involved in the phosphorylation of this protein., THE presence of this protein and its phosphorylated derivative in node-negative breast cancer shows nuclear localization is associated with a better prognosis., independent and cooperative activation of chromosomal c-fos promoter by STAT3, STAT3 is constitutively activated in Crohn's patients but not in healthy volunteers, Hematopoietic CD34+ cells secreted IL-15 that, through autocrine/paracrine loop distinct signal pathways, activated NF-kB in bone marrow and cord blood progenitors, and activated STAT3 and STAT5 in peripheral G-CSF-mobilized and BM progenitors only., GRIM-19 protein specifically suppresses Stat3 protein activity via functional interaction., gp120 induces activation of STAT1, STAT3, and STAT5 in CD4+ cells of lymphocyte or monocyte/macrophage lineages., We conclude that IL-6 may promote cervical tumorigenesis by activating VEGF-mediated angiogenesis via a STAT3 pathway., activation of STAT3 was dependent on Ser727 phosphorylation, in the absence of detectable Tyr705 phosphorylation; expression of human STAT3 in murine macrophages rescued inhibition of human Mcl-1 promoter gene activation and cell death induced by NaSal, RET/PTC associates with STAT3 and activates it by the specific phosphorylation of the tyrosine 705 residue. STAT3 activation by the RET/PTC tyrosine kinase is one of the critical signaling pathways for the regulation of specific genes., Inhibition of this protein with a decoy oligodeoxyribonucleotide abolishes head and neck cancer cell growth., G protein-coupled receptors activate STAT3 via G alpha(16), a G alpha subunit which is primarily expressed in hematopoietic cells., Analysis of this protein's pathway in myeloma, ubiquitylation and degradation by mumps virus V protein prevents responses to interleukin-6 and v-Src signals and can induce apoptosis in STAT3-dependent multiple myeloma cells and transformed murine fibroblasts, Results provide evidence that interleukin-13 induces p38 MAP kinase phosphorylation and activation, which regulates Stat1 and Stat3 serine 727 phosphorylation., Data suggest there is no defect in the JAK/STAT pathway in the tested melanoma cell lines, and that interferon resistance must be mediated through other components., Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system., We now demonstrate ligand-independent activation of Stat3 by high cell density in multiple cancer cell lines.Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity., AR and PIAS3 regulate the STAT3-mediated transcriptional activity by their physical protein-protein competition on STAT3, STAT3 has a role in the pathogenesis of human chronic myelogenous leukemia, Stat1 and Stat3 exist as stable homodimers prior to activation, Stat3 has a role in transducing survival signals downstream of tyrosine kinases such as Src, EGF-R, and c-Met, as well as cytokines such as IL-6, in human nonsmall cell lung cancers, STAT1 and STAT3 may, at least in part, mediate angiotensin II-induced TIMP-1 mRNA expression in human renal proximal tubular epithelial cells, implicating a role of the STAT signaling pathway in pathogenesis of renal tubulointerstitial fibrosis., STAT3 activation associated with better disease-free survival in nasopharyngeal carcinoma, STAT3 activation is required for keratinocyte differentiation in normal human stratified squamous epithelium, Stat3 is transactivated via IL-6 response elements on fibrinogen promoters with participation of additional transcription factors, Nef activates STAT3 through a mechanism mediated by the release of soluble factor(s) in human monocyte derived macrophages., Differentiation-dependent expression of STAT3 may modify responses to growth factors in the cancers of the head and neck., The activation of signal transducer and activator of transcription 3 (Stat3) is obligatory for the survival of INA-6 multiple myeloma cells., Signal transducer and activator of transcription 3 is the most potent activator of acute-phase gene transcription., STAT3 is stimulated by Galpha16 via a c-Src/JAK- and ERK-dependent mechanism, STAT3/NF-kappaB p65 cross-talk activated by IL-1 via TRAF6., role in regulating expression of hepatocyte growth factor, Specific DNA binding activity of two STAT3 variants (STAT3alpha and beta) was observed in immature trophoblasts and appeared to be lost in term placentae. The malignant phenotype of choriocarcinoma cells coincides with a high degree of STAT3 activity., Although the data show that STAT3 is required for the majority of IL-10 functions, there are elements of the anti-inflammatory activity of IL-10 that are STAT3 independent., STAT3 recombinant fusion protein shuttles continuously between the cytosol and the nucleus in unstimulated cells, interaction of Stat3 and ZBP-89 may be crucial for overcoming the effects of the repressor ZBP-89, which suggests a novel mode for Stat3 gene activation., In the luciferase assay, ATBF1 was found to have no influence on STAT3 signaling induced by IL-6 stimulation, but it did synergistically enhance PIAS3 inhibition of activated STAT3., Taken together, our findings demonstrate that constitutively activated Stat3 up-regulates HSP27 and may facilitate phosphorylation of HSP27 at serine residue 78., G-CSF like IL-10 inhibits LPS-induced TNF-alpha production in human monocytes through selective activation of STAT3 and the immunomodulation observed in vivo by G-CSF administration may be partly ascribed to the direct effect of G-CSF on monocyte function, MITF and STAT3 cooperatively induce c-fos, resulting in cellular transformation, STST3 activation is mediated by EGFR and c-Src and facilitated by Pyk2, interactions of the phosphotyrosine ligands with specific amino acid residues of Stat3 SH2 region are described, Stat3 activity is upregulated during the confluence-mediated growth arrest by a signalling mechanism that requires JAKs, IL-10 gene regulation in colon tumor cells is mediated by STAT3, which is phosphorylated after the binding of IL-6 the IL-6 receptor., N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) from P. aeruginosa ablates STAT3 activity in breast tumor cells., cells from multiple myeloma patients express constitutively active NF-kappaB and STAT3, and suppression of these transcription factors inhibits the survival of the cells, STAT3 signaling supports gastric cancer cell survival in association with survivin expression., a profound in vivo activation of STAT3 is observed in mycosis fungoides (MF) tumors but not in the early stages of MF. STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL., the c-src kinase/STAT3 pathway has a role in Ox-PAPC-mediated IL-8 expression in endothelial cells, STAT3gamma is rapidly generated from STAT3alpha by limited proteolysis with granule-derived serine proteases during preparation of neutrophil lysates, Inhibition of STAT3 reduced the motility of ovarian cancer cells in vitro, and activated STAT3 localized not only to nuclei but also to focal adhesions in these cells., STAT3 directly contributes to the high level of TIMP1 expression in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma., Constitutive activation of Stat3 may play an important role in the tumorigenesis of colorectal carcinoma, results show STP-A11 (Saimiri transforming protein oncogne of Herpesvirus saimiri subgroup A strain 11) independently targets two important cellular signaling molecules, Src and Stat3; these proteins cooperate to induce STP-A11-mediated transformation, expression of STAT-3 induced by Epstein-Barr virus (EBV) LMP-1 (latent membrane protein) and may be part of the viral programming that regulates viral latency and cellular transformation, constitutive activation of Akt and NFkappaB, but not Stat3, contributes significantly to the progression of diffuse gliomas, importance of STAT3 signaling in the regulation of neuronal growth and differentiation by the mu-opioid receptor., Although the methylation frequency of SOCS-1 is low, the data of Fujitake et al. indicate role of JAK/STAT/SOCS pathway in gastrointestinal tumorigenesis., We found that the amino terminal domain of STP A11 is required for both STAT3 interaction and activation, and that physical interaction is required for STAT3 activation., STAT3 interacts with STRA13 and modulates transcription of STAT3-dependent targets., Inhibition of Stat3 activity by TEL represents a novel mechanism regulating the Stat3 signaling pathway, Stat3 mediated by c-Met is frequently associated with the progression of oral squamous cell carcinoma, Existence of a factor in mouse feeder layer cells that acts to maintain huma embyonic stem cells cell renewal in a STAT3-independent manner., data reveal an important role for MgcRacGAP in STAT3 activation, and demonstrate that MgcRacGAP regulates IL-6-induced cellular differentiation in which STAT3 plays a pivotal role, Promotes the initiation of transcription but also regulates chromatin remodeling and transcription elongation through its interaction with BRG1 and cdk9., Detailed pathway analysis revealed that BM stromal cells stimulate STAT3 via the IL-6R, and MEK1/ERK1 pathways, via IL-6R-independent mechanisms, STAT3 forms a related complex in cells upon oxidative stress. interacting at cysteine 259., constitutively active Stat3 upregulates MEK5 in the breast epithelial cells. MEK5 may be one of the Stat3-regulated genes and plays its essential roles in oncogenesis, STAT3 activation is capable of initiating intracellular antiviral pathways, Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3beta, Ectopic expression of wild-type but not Thr(p+1loop)-->Met substituted EPH family members constitutively phosphorylated STAT3, The conserved STAT3 region from 752 to 761, called STAT3 CR2, plays critical roles in STAT3-dependent transcription by recruiting SRC-1 and allowing Ser727 phosphorylation., Cold ischemia and reperfusion induced increased levels in liver transplantation., The STAT3 was detected in cytoplasm and nucleus and in carcinomas it was limited to cytoplasm., Coordination between Stat1 & Stat3 activation determines GTPCH I induction. Stat1 & NF-B activation, coordinated with the lack of Stat3 activation, accounts for cytokine-stimulated GTPCH I induction in endothelial cells., The N-terminal part of the 1st intracellular loop (ICL) is needed to activate Jak2 after SDF-1alpha binding to CXCR4, leading to phosphorylation of only one cytoplasmic Tyr, present at the C terminus of the 2nd (ICL), which triggers STAT3 activation., suppressor of cytokine signaling 3 regulates Hepatocyte growth factor-induced keratinocyte migration by inhibiting STAT3 phosphorylation, an increased transcriptional level of constitutive STAT3 may be related to the suppressive regulation of the apoptotic pathway in intrinsically chemo-resistant NSCLC cells., acetylation of Stat3 can stimulate its sequence-specific DNA binding ability and transactivation activity., results show that Hepatitis C virus(HCV)-induced activation of STAT-3 is mediated by oxidative stress and influenced by the activation of cellular kinases; results also suggest a potential role of STAT-3 in HCV RNA replication, Lys685 acetylation critical for Stat3 to form dimers required for cytokine-stimulated DNA binding & transcriptional regulation, to enhance transcription of cell growth-related genes & to promote cell cycle progression after treatment with oncostatin M, one of the major roles of Stat3 in the G-CSF signaling pathway is to augment the function of C/EBPalpha, which is essential for myeloid differentiation, TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells., Results indicate that SOCS-7 is a dysregulator of prolactin, leptin, and growth hormone signaling and that its mode of action is a variation of SOCS protein inhibition of cytokine-inducible STAT3 and 5-mediated signal transduction., Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line, IL-6-induced STAT3 activation in human prostate cancer cell lines., HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE regulate Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas, pharmacological agents that can selectively reduce the P-STAT3 levels in human cancer cells result in tumor apoptosis and growth inhibition, previously uncharacterized genes induced by Stat3 implicated in signaling pathways common to both wound healing and cancer including cell invasion and migration, angiogenesis, modulation of coagulation, and repression of interferon-inducible genes, Findings provide evidence that STAT 3 signal activity in head and neck carcinomas, which is partially responsible for proliferative activity, can be controlled via the EGFR., STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, extracellular signal-dependent nuclear transport of STAT3 is mediated by various importin alphas, importin beta, and Ran, demonstrate using RNAi that Stat3 activation is necessary in the invasive phenotype of trophoblast cells and can be controlled via Leukemia Inhibitory Factor (LIF), cIAP2 expression is up-regulated by IFN-alpha and IFN-gamma through the JAK2-STAT3 pathway, and increased expression of the cIAP2 protein may contribute to an IFN-alpha- and IFN-gamma-mediated antiapoptotic effect on human neutrophils., STAT3 may transform cells by inducing epigenetic silencing of SHP-1 in cooperation with DNMT1 and histone deacetylase 1, interacts with dengue-2 virus NS1 protein, activation by leptin is associated with gastric cancer cell proliferation, STAT3 signaling pathway is involved in IL-6-induced neuroendocrine(NE) differentiation and that p38 MAPK is associated with IL-6-stimulated growth regulation in NSCLC-NE cells., The physiological role of Stat3 in anaplastic large cell lymphomas and the effects of inhibition of expression of the gene on tumorigenesis is reported., Activation of Stat3 signaling in respiratory epithelial cells of STAT3 transgenic mice protects against hyperoxia-induced inflammation and injury in the lung., STAT3 signaling is important in the pathogenesis of classical Hodgkin lymphoma, Stat3 is an important component of a pathway emanating from tumor antigen of Simian Virus and leading to neoplastic conversion, Data show that medroxyprogesterone acetate treatment of mammary tumor cells up-regulated Stat3 protein expression and induced rapid, nongenomic Stat3, Jak1, and Jak2 tyrosine phosphorylation., Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma., These suggest that JNK and STAT3 may constitute a universal signaling pathway to mediate adiponectin's pathophysiological effects on metabolic syndrome and cancer., Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression, STAT3 physically interacts with epidermal growth factor receptor in the nucleus, leading to transcriptional activation of inducible nitric oxide synthase., Results identify a cohort of STAT3 targets that may mediate its role in oncogenesis in breast and prostate cancer., results demonstrate for the first time that prostacyclin receptor activation by cicaprost can lead to STAT1 and STAT3 phosphorylations via signaling pathways involving pertussis toxin-insensitive G proteins, ERK and JNK, Stat3 is required for both basal and growth signal-induced expression of HIF-1, STAT3 has a role in colorectal tumor growth, Growth factors and cytokines stimulate hTERT expression in primary human cells in a STAT3-dependent manner. STAT3 is a key regulator of hTERT expression in both normal and tumor cells., Association between STAT3 and ARHI as well as the functional inhibition of STAT3 transcriptional activity by ARHI suggests a novel mechanism through which a putative tumor suppressor gene can inhibit STAT3 activity in breast and ovarian cancers., constitutive Stat3 signaling may be one of the key upstream regulators to induce downstream proteins which may play important roles in Stat3-mediated oncogenesis in breast cancer, STAT3 can participate in neoplastic transformation through novel and non-canonical mechanisms [review], End-stage hepatitis c and alcoholic liver cirrhosis is characterized by impaired Stat3 DNA-binding possibly through up-regulation of Pias3., repression of tumor protein p53 expression by Stat3 is likely to have an important role in development of tumors, Results suggest a connection between leukemia inhibitory factor-driven STAT3 activity and invasiveness of choriocarcinoma and trophoblast cells., These data demonstrate that Arg-214/215 are involved in CRM1-mediated STAT3 nuclear export and the regulation of STAT3 activity., NF-kappaB and STAT3 are activated by proteolysis inducing factor in human Kupffer cells and monocytes, AKT1 is a direct target gene of Stat3 and contributes to Stat3 anti-apoptotic function, Inhibition of STAT3 signaling in colon carcinoma tumors and cell lines induces apoptosis and cell cycle arrest of colon carcinoma cells., Study proved that overexpression of STAT3(WT) could augment the migration of BEL-7402 cells, while STAT3(CYF) could decrease the migration., We provide evidence that STAT3 plays an essential role in cytokine-driven SAA expression, although the human SAA gene shows no typical STAT3 response element, Cyclooxygenase-2-dependent activation of STAT3 by interleukin-6 has a role in non-small cell lung cancer, acetylation-deacetylation reaction as a novel signaling mechanism controlling the IL-6-STAT3 pathway in the hepatic acute phase response, STAT3-mediated transcriptional activation in inhibited by Daxx, Stat3 downregulation in vSrc transformed NIH3T3 cells or in breast cancer lines with activated Src induces apoptosis, but in normal cells Stat3 inhibition at post-confluence causes apoptosis while in sparsely growing cells it induces growth retardation, STAT3 and PY-STAT3 in the cytoplasm have roles in endocytosis, Our results suggest that p-ser727-STAT3 may be involved in the pathogenesis of breast cancer in an ER-dependent manner., SOCS-1 methylation status can differentially affect STAT3 activation, This review of head and neck squamous cell carcinoma discusses how STAT3 alters the tumor cell cycle, prevents apoptosis, and mediates proliferation and survival of tumor cells., findings demonstrate that Stat3 plays a critical role in the tumorigenesis, but not in the cell survival, of cutaneous squamous cell carcinoma cells and suggest that additional pro-apoptotic signals are necessary for the induction of apoptosis, there are tissue-specific differences in IL-6-receptor-gp130-coupled signaling which limit the extent of Stat3 activation and gammaFBG expression during lung inflammation, Tax-mediated regulations of IL-6R and sIL-6R observed in HTLV-I-associated disorders may contribute to proliferation of HTLV-I-infected T cells through activation of inducible STAT3, Activation requires the catalytic activity of Brk., changes in the relative expression and activation of STAT1 and STAT3 that occur during immune responses determine the nature of cellular responses to type I IFNs, Stat3 is involved in keloid pathogenesis. Inhibitors of Stat3 may be useful therapeutic strategies for the prospective treatment of keloid scars., Stat3 undergoes proteolytic processing by caspases that reduces its expression and leads to the formation of cleavage fragments that may modulate Stat3 transcriptional activity, Stat3-mediated p100 processing to p52 requires activation of Stat3 by the acetyltransferase activity of cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300, To our knowledge, this is the first study on the poor prognosis of p-STAT3 in human colorectal adenocarcinomas. These findings suggest that expression of p-STAT3 is related to tumour invasion and poor prognosis of human colorectal adenocarcinoma., role for IL-11 via pSTAT3 and SOCS3 in initiating and progressing decidualization, Silencing Stat3 expression by small interfering RNA (siRNA) abrogated BCL3 expression by IL-6, Haplotypes of STAT3 predict cardiovascular disease in renal dialysis patients., Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma., Atiprimod blocked Stat3 activation and inhibited colony-forming cell proliferation in acute myeloid leukemia cells., Mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation., IL-6 induces Protein S expression via STAT3. Possible function for IL-6-induced Protein S expression in cell survival., STAT3 activation by IL-6 provides an antiapoptotic advantage in human cord blood cells CD34+ cells, essentially owing to the expression of bcl-2., STAT3 binds in vitro to 2 STAT3 SIE/GAS-binding sites identified in promoter 1 and enhancer 1 of the DNMT1 gene, mutant JAK2 contributes to myelofibrosis with myeloid metaplasia pathogenesis by constitutively phosphorylating STAT3 and diminishing myeloid cell apoptosis, These reuslts show a significant association between the expression of the phosphorylated/active form of STAT3 (pSTAT3) and that of TIMP1., Stat3 binding at position -1024 of the endothelial nitric-oxide synthase (eNOS) promoter mediates Stat3 inhibition of eNOS promoter activity., Phosphorylation in trophoblasts or blood mononuclear cells activated with lipopolysaccharide or phytohemagglutinins showed phosphorylation of this protein., PDTC downregulates IL-6-induced STAT3 activation by altering the stability of STAT3-Hsp90 complex, observed a reperfusion time-dependent increase in the tyrosine phosphorylation of STAT1 and STAT3 at residues 701 and 705, respectively, which was dramatically reduced by tempol, STAT3 is a key effector of baseline hepcidin expression and during inflammatory conditions., results suggest that phospho-Stat3 expression might be associated with angiogenesis, anti-apoptosis, and tumor progression in gastric cancer, The activated (phosphorylated) Stat3 is overexpressed in most paclitaxel-resistant ovarian cancer cells. The interruption of Stat3 signaling could reverse resistance to paclitaxel and perhaps other chemotherapy agents in human cancer., These results suggest a relevant role for STAT5 and Bcl-xL as apoptosis-regulatory proteins in the pathogenesis of lung cancer, and overexpression of both Neu and activated STAT3, could be related with the proliferation rate in lung carcinoma cells., there is a cross-talk between the NFkappaB and the STAT3 signaling systems, and HNSCC may result from the aberrant activity of a signaling network, STAT3 activation by G alpha(s) distinctively requires protein kinase A, JNK, and phosphatidylinositol 3-kinase, The Ras/Raf-1/MEK1/ERK cascade culminates in nicotine up-regulated expression of the gene encoding STAT-3, whereas recruitment and activation of tyrosine kinase JAK-2 phosphorylates it., To determine the prosurvival function of STAT3 vs STAT5 within the same tumor model, genes were profiled in STAT3- or STAT5-depleted human lymphoblastic lymphoma-derived cell line YT cells by apoptosis-specific microarrays, Chromium activates epithelial cell Lck to signal for prolonged STAT3 activation and transactivation of interleukin-6, an important immunomodulator of lung disease progression, Leptin and TGF-beta1 synergistically augmented activation of signalling components of mitogen-activated protein kinase (MAPK), STAT3 and Smad but did not modulate the expression of LEPR-B., The STAT3 pathway is involved in Cdk5-dependent proliferation of medullary thyroid cancer cells through Ser-727 phosphrylation., Activated STAT3 translocates to the nucleus of KSHV-infected endothelial cells, where it can bind to STAT3-specific DNA elements and can activate STAT3-dependent promoter activity., BRG1 is constitutively present at IL-6-responsive promoters and is required for STAT3 recruitment, downstream histone modifications, and IL-6-induced chromatin remodeling., STAT3 activity can suppress both IL-6 and tumor necrosis factor production in lipopolysaccharide-stimulated macrophages., activation of STAT3 may play an important role in the tumorigenesis of gastric adenocarcinoma, These data suggest that STAT3 signaling is an important common element and may contribute to the remodeling and adaptation of skeletal muscle following resistance exercise., tumor samples from FMTC patients showed strong nuclear staining of phosphorylated ERK1/2 and Ser(727) STAT3; FMTC-RET mutants activate a Ras/ERK1/2/STAT3 Ser(727) pathway, which plays an important role in cell mitogenicity and transformation., let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes, The expression of STAT3 was positively related to that of Survivin and Ki67 in in nasal NK/T cell lymphoma., SOCS-3 epigenetic silencing is responsible for sustained IL-6/STAT-3 signaling and enhanced Mcl-1 expression in cholangiocarcinoma, Cell confluence-induced Stat3 signaling is induced in Madin-Darby canine kidney epithelial cells in triggering dome formation through sodium hydrogen exchanger-3 augmentation., Myocardial STAT3 protein levels are reduced and serum levels of activated cathepsin D and 16 kDa prolactin are elevated in postpartum cardiomyopathy patients., Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers., In chronic hepatitis C, liver fibrosis progression is characterized by a continuous decline in Stat3 DNA-binding activity related to overexpression and progressive interaction of Pias3-Stat3., STAT-3 activation by DFMO is at least in part mediated through the PKA pathway, This review article discusses the role of STAT3 in cancer in detail as evidenced by its constitutive activity in tumor cells, and its regulation of genes that mediate proliferation, suppress apoptosis or promote angiogenesis., silibinin inhibits constitutively active Stat3 and induces apoptosis in DU145 cells, and thus might have potential significance in therapeutic intervention of this deadly malignancy., CYCLIN D1 may be a target gene for leptin mediated growth stimulation of breast cancer cells and molecular mechanisms involve activated Stat3, STAT3 is a substrate of receptor protein tyrosine phosphatase T, Increasing the protein levels of the signal transducer and activator of transcription 3 (Stat3) led to Stat3-androgen receptor (AR) complex formation in response to epidermal growth factor (EGF) and interleukin-6 (IL-6) stimulation., found 3 specific patterns of pSTAT-3 and pSTAT-5 expression, CCL2 mediates fibroblast survival by inhibiting apoptosis through IL-6/STAT3 signaling, IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3., Constitutively activated STAT3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through ITGB6., STAT3 was overexpressed in laryngeal carcinoma. Activation of STAT3 was significantly related to the clinical stage and lymph node metastasis., Activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and silencing of the STAT3 gene with RNAi may be a useful anti-invasive therapeutic option in pancreatic cancer., Aberrant activity of STAT3 in colorectal neoplasms is linked to malignant tumor progression through upregulated expression of matrix metalloproteinases MMP-1, -3, -7, and -9., antitumor activity of S3I-201 is mediated in part through inhibition of aberrant Stat3 activation, administration of IL-6 could activate receptor gp80/gp130 signaling pathways including downstream extracellular signal-regulated kinase 1/2 and STAT3 phosphorylation in EPCs., STAT3 and PKC differentially regulate telomerase activity during megakaryocytic differentiation of K562 cells., Blockade of the gp130 receptor or sequestration of the interleukin-6 (IL-6) ligand led to a decrease of phosphorylated Stat3 levels in breast cancer., GM-CSF-stimulated CD34(+) cell proliferation is regulated by the JAK/STAT3/survivin signaling pathway., in addition to activating NF-kappaB/p52, LIGHT also activates Stat3 through the NIK pathway, These results indicate that expression of the gamma-fibrinogen gene is mainly controlled by the strength of late phase STAT3 activation, which in turn is negatively regulated by the extent of interleukin-1beta-mediated NF-kappaB activity., Stat3 has a role in the photodynamic reaction in cells and tumors, The activation of MMP-9 promoter is dependent upon interactions of Fra-1/c-Jun with Stat3., Statistically analyzed distributions of the proteins reflected functional dependences among STAT3, HIF-1alpha, EPO and EPOR in cellular signal conduction., STAT3 polymorphism has a role in patient resopnse to IFN-alpha therapy in patients with metastatic renal cell carcinoma, These observations suggest that SOCS6 is composed of at least two functional domains required for its biological role in localizing and degrading Stat3 in the nucleus., GRIM-19 suppresses constitutive STAT3-induced cellular transformation in vitro and in vivo by down-regulating the expression of a number of cellular genes involved in cell proliferation and apoptosis, The high expression of STAT3 and the low expression of GRIM-19 co-exist in colorectal carcinoma, and may be related to malignant transformation and abnormal proliferation of cells., Since STAT3 reactivation occurred in 14 of 15 solid tumor cell lines, dasatinib combined with Janus-activated kinase inhibitors may have widespread application in cancer treatment., Amino acid residues required for physical and cooperative transcriptional interaction of STAT3 and AP-1 proteins c-Jun and c-Fos., Single nucleotide polymorphism variations are not indicative of obesity and insulin resistnce., In actinic cheilitis, STAT-3 expression depends on the degree of dysplasia, and STAT-3 activation is dysregulated compared with normal tissue, Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation., Data provide direct evidence for IL-6 induced "signal transduction" by STAT3 from the plasma membrane to a cytoplasmic membrane destination for yet to be elucidated function(s) in the cytoplasm including prolongation of signaling and/or cross talk., STAT 3 and androgen receptor signaling are inactivated in androgen-dependent LNCaP cells after administration of Saw Palmetto, The up-regulation of COX-2, p-Stat3, and p-Stat5 may be correlated to the carcinogenesis of ESCC. The activation of Stat3 is correlated to the aggressive behavior of ESCC., dominant-negative mutations in the human signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem hyper-immunoglobulin E syndrome (HIES), phosphorylated STAT3 and Akt play an important role in pathogenesis of malignant tumors of the epidermis, Sodium arsenite dose dependently alters STAT3 and JAK2 activities via Bcl-6 and this may have a role in arsenic-associated carcinogenesis., Stat3 has an important role in the early stages of epithelial carcinogenesis as well as a novel role in malignant progression of skin tumors in a transgenic mouse model., STAT3, Runx2, and steroid receptor coactivator-1 are critical molecules in mediating leptin-stimulated cell osteogenesis in TOLF (thoracic ossification of ligament flavum), STAT3 tyrosine phosphorylation occurs in preformed transducer complexes that can be activated in the absence of intact lipid rafts or caveolin., The combined data suggest that STAT3 tyrosine phosphorylation occurs in preformed transducer complexes that can be activated in the absence of intact lipid rafts or caveolin., in angiosarcoma, significant correlation was seen between phosphorylated-STAT3 and cyclin D1 but not between phosphorylated Akt and cyclin D1, The role of the Stat3 pathway in the regulation of Il8 transcription by Ox-PAPC in vitro and in atheroclerosis in vivo is reported., Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis., ET Patients lacking the JAK2V617F mutation displayed significantly lower expression of the JAK/STAT target genes Pim-1 and suppressor of cytokine signaling-2. In addition, JAK2V617F-negative patients showed lower levels of STAT3 phosphorylation, siRNA specifically and efficiently blocks the constitutively activated STAT3 signaling pathway in human esophageal squamous carcinoma cells., strong expression of cytoplasmic inactive STAT3 in NSCLC and malignant mesothelioma cases implies a major role for STAT3 in tumor motility, invasion, and metastasis via a nontranscriptional pathway, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation, Ursolic acid is a novel blocker of STAT3 activation that may have a potential in prevention and treatment of multiple myeloma and other cancers., ATF2/STAT3 signaling pathways are activated and may play a role in development of eccrine porocarcinoma and eccrine poroma., PKCepsilon activation is essential for constitutive activation of Stat3 and prostate cancer progression., The IL-6/STAT3 antiapoptotic pathway is induced by short exposure to bile acid cocktail and low pH., IFNalpha is able to interfere with IL-6 signaling by inhibiting STAT3 activity and the abrogation of STAT3 activity accounts for the ability of IFNalpha to induce apoptosis in myeloma cells., Mutations in STAT3 underlie sporadic and dominant forms of the hyper-IgE syndrome. Eighteen discrete mutations, five of which were hot spots, were predicted to directly affect the DNA-binding and SRC homology 2 (SH2) domains., Together, these data demonstrate that NDRG2 expression in breast cancer cells is able to inhibit STAT3 activation via SOCS1 induction in a p38 MAPK dependent manner., low p-STAT3 in GCs may account for decreased fertilization, implantation, and pregnancy rates of in vitro fertilization in polycystic ovarian syndrome women, CTR9 participates in the transcription of IL-6-responsive genes through the regulation of DNA association of STAT3 and modification of histone methylation, In breast cancer stem-like cells, the STAT3 pathway was found to be positively regulated by mTOR signaling, whereas PTEN served as a negative regulator of both STAT3 and mTOR signaling., EGFR induces expression of IRF-1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells, Observations suggest that suppression of Stat3 signaling may provide a potential therapeutic approach to overcoming DOX resistance in metastatic breast cancer cells., The activation of AKT and NF-kappaB, but not STAT3, significantly contributes to the progression of breast cancer., Following cell exposure to IL-15, phosphorylation of STAT5 was predominantly observed, whereas, following stimulation with IL-21, there was predominant STAT1 and STAT3 activation., define a second oncogenic pathway, STAT3 activation, which operates in activated B-cell-like Diffuse large B-cell lymphoma, an IL-6-inducible STAT3 and CDK9 binding to the proximal gamma-FBG promoter as well as increased loading of RNA Pol II, Thus the c-myc P2E behaves as a dual-purpose STAT3 element with anomalous characteristics in HepG2 cells., the potential mechanism by which cell-cell contact initiates STAT3 activation., human breast cells are a uniquely permissive environment for HGF transactivation by Src/Stat3 which may allow for the inappropriate activation of HGF transcription during the early stages of breast transformation, We conclude that Stat3 binding is important for MASP2 promoter activity., Blocking Hsp90 disrupts IGF-I and IL-6-induced proangiogenic signaling cascades by targeting IGF-IR and STAT3 in pancreatic cancer, Although this is a very rare case of HIV-1-integrated lymphoma, these data suggest that up-regulation of STAT3 caused by HIV-1 integration resulted in the development of B cell lymphoma in this special case., anti-apoptotic effects of STAT3 signaling in gastric cancer cells by enhancing Akt activation, Bad phosphorylation and Bcl-xL is mediated by REG Ialpha expression, Reduced endometrial pSTAT3 and IL-11 may be involved in secretory transformation of glandular epithelium during receptivity. Reduced IL-11 production and STAT3 phosphorylation may contribute to unexplained infertility in some women., A model for binding of phosphopeptides to SH2 domain of STAT3 was presented., YC-1 inhibited Stat3 activity by enhancing the polyubiquitination of P-Stat3(705) induced by cisplatin., EGFR could activate the gp130/JAK/STAT3 pathway by means of IL-6 upregulation in primary human lung adenocarcinomas, making this pathway a potential target for cancer treatment., The expression of STAT3 and p38 was positively correlated with the degree of dysplasia in sporadic colorectal tubular adenoma., the astroglial differentiation effect of AICAR on neural stem cells was acting independently of AMPK and that the JAK-STAT3 pathway is essential for the gliogenic effect of AICAR., SN acts directly on neurons after hypoxia and ischemic insult to further their survival by activating the Jak2/Stat3 pathway., Regulates ATP-binding cassette transporter 3 (ABCA3) expression in vivo and in vitro., STAT3 mediates resistance to ATP depletion-induced apoptosis of proximal tubular epithelial cells, which may be a potential target in treatment of renal ischemic injury., Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma, variations in cell density can profoundly modify the extent of JAK-mediated persistent STAT3 phosphorylation; however, STAT3 activation was not sufficient to provide critical growth and survival signals in melanoma cell lines, The Ang II/Rac1/STAT3 pathway is an important signaling pathway in the atrial myocardium to mediate atrial structural remodeling, and losartan and statin may be able to reverse Ang II-induced atrial structural remodeling in atrial fibrillation., a network involving signal coactivation of NF-kappaB and STAT3, differentially modified by p53 inactivation or mutation, promotes altered BAX/BCL-XL expression and cell survival in HNSCC., potential coordinative effects of Wnt, NF-kappaB and/or Stat3 activation on gastric cancer formation presumably by promoting the transcription of their common target genes., Abnormal STAT3 signalling in T cells from Sjogren's syndrome patients., Sp1 recruits ATF3, c-Jun, and STAT3 to obtain the requisite synergistic effect in neuronal injury through DINE neuronal injury-inducible gene, Interferon gamma induces XAF1 and Noxa expression and potentiates apoptosis by STAT3 activation, autoregulation of DeltaNp63 gene transcription is mediated through activation of STAT3 and its subsequent binding to the STAT3RE., Results suggest that STAT3 siRNA can inhibit the invasion ability of colon cancer cells through inducing anoikis, which antiapoptotic genes survivin and Bcl-xL contribute to regulation of anoikis., LMP1 stimulated STAT3 Tyr 705-dependent nuclear accumulation, as well as the phosphorylation of STAT3 at both Tyr 705 and Ser 727., identify leptin/STAT3 signaling as a novel pathway for survivin expression in breast cancer cells, an essential role of the SH2B1 variants in the activation of the Src kinase and the resulting mitogenic response--extending to phenotypic cell transformation and involving the established Src substrate STAT3., HOXA1 partially mediates oncogenic transformation of the immortalized human mammary epithelial cell through modulation of the STAT3 and STAT5B pathways., pSTAT3 is a potential biomarker of melanocytic transformation and progression, Nuclear accumulation of STAT3 activation by IL-6 plays a key role in iNOS expression and resultant DNA damage, leading to EBV-mediated Naso-Pharyngeal Carcinoma(NPC)., Novel mitogenic signaling pathway in airway smooth muscle cells leading from PDGF to Stat3 and cell cycle gene regulation., Theses findings illustrate the biologic significance of JAK1, 2/STAT3 signaling in colorectal cancer (CRC) progression and provide novel evidence that the JAK/STAT3 pathway may be a new potential target for therapy of CRC., Stat1/3 directly controls promoter P1 of the CASR, and the Stats indirectly regulate promoter P2 of the CASR via Sp1/3 in response to IL-6, STAT3, Twist, and AKT2 form a functional signaling axis to regulate pivotal oncogenic properties of cancer cells, STAT3 activation functionally mimicked IL-21 treatment and that STAT3-mediated BLIMP1 up-regulation occurred despite high BCL6 expression levels, STAT3 activation is independent of the EGFR/MEK/ERK signaling pathway, JAK-STAT3 signaling pathway participates in regulating the invasion and metastasis of human breast cancer., STAT3 activation mediates COX-2 expression and ischemic tolerance., Src-dependent STAT-3-mediated VEGF expression is a major mechanism of 14,15-EET-induced angiogenesis, HER2-dependent transcriptional upregulation and protein secretion of MMP-7 are mediated by activated STAT3., The C-28 methyl ester of the oleane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) inhibits activation of the JAK1-->STAT3 pathway by forming adducts with both JAK1 and STAT3., STAT3 enhances invasiveness of tumours and trophoblast cells., PIM1 kinase plays a critical role in the STAT3 --> PIM1 --> NFkappaB stress response pathway, Single nucleotide polymorphism in STAT3 gene is associated with ulcerative colitis, HA binding to tumor cells promotes Nanog protein association with CD44 followed by Nanog activation and the expression of pluripotent stem cell regulators, and forms a complex with Stat-3 in the nucleus leading to Stat-3 and MDR1 activation, Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells., lower levels of pSTAT3 were found in the nuclei of hepatitis E virus ORF3-expressing Huh7 human hepatoma cells stimulated with EGF. This results in downregulation of the acute-phase response, a major determinant of inflammation in the host., Results do not support a major role for STAT3 variants in BMI, obesity and insulin resistance in an adult male population., The Stat3-activating Tyk2 V678F mutant does not up-regulate signaling through the type I interferon receptor but confers ligand hypersensitivity to a homodimeric receptor, Mutations are implicated in hyper-IgE syndrome., Epigallocatechin-3-gallate suppresses the pathological characteristics of keloids through inhibition of the STAT3-signaling pathway., These results indicate that the IL-6 family of cytokines modulates STAT3 activation by desumoylation and inactivation PML through SENP1 induction., Stat3 is involved in metastatic behavior of human prostate cancer cells and may provide a therapeutic target to prevent metastatic spread of primary prostate cancer., persistent activation of STAT1, STAT3, and STAT5 correlate with resistance to vorinostat in lymphoma cell lines, nuclear STAT3 expression is associated with poor patient prognosis in the intestinal subtype, a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within colorectal carcinomatumours., Y14 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing the tyrosine-phosphorylation of STAT3., KLF11 may interfere with glucose homeostasis in a Danish general population and that STAT3-mediated up-regulation of KLF11 transcription was impaired by the -1659G>C variant., Down-regulating signal transducer and activator of transcription 3 (STAT3) expression by short hairpin RNA in Smad4-deficient cells prevented TGFbeta-induced invasion, Platelet-derived growth factor-induced cell growth, migration, and IL8 secretion in corneal fibroblast involve the JAK2-STAT3 signaling pathway., This study uncovers a novel link between STAT3 and interleukin 8, the deregulation of which plays a key role in the malignant behavior of glioblastoma cells., In addition, STAT3 knockdown inhibited anchorage-independent growth and induced apoptosis in CAOV3 cells, and decreased tumor growth in nude mice implanted with ovarian cancer cells., Overexpression of phosphorylated-ATF2 and STAT3 in cutaneous squamous cell carcinoma, Bowen's disease and basal cell carcinoma., parvovirus B19 NS1 protein modulates inflammatory signaling by activation of STAT3/PIAS3 in human endothelial cells, There is a marked increase in STAT3 activation in many forms of glomerulonephritis. The correlation of STAT3 activation with clinical and histologic parameters suggests that this pathway plays an important role in the pathogenesis of kidney disease., IL-6 treatment induced MUC4 expression through the gp130/STAT3 pathway, indicating the direct role of IL-6 on the activation of the intestinal mucin gene MUC4 in gastric cancer cells, nonoverlapping, sequential activation of STAT3 and STAT5 selects for multilog expansion, programming, and dendritic cell DC1 polarization of tumor-competent DCs from CD34(pos) cells, Data show that platelet-derived growth factor-BB induces mesenchymal stem cell proliferation via activation of the Jak2-Stat3 transcription cascade., a failure of CD4+ T cells harboring heterozygous STAT3 mutations to generate interleukin 17-secreting cells due to a failure to express sufficient levels of the Th17-specific transcriptional regulator retinoid-related orphan receptor t., IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo., The importance of STAT3 signaling in maintenance and survival of medulloblastoma cells., heterozygous STAT3 mutations were identified in 34 of 35 unrelated Hyper-IgE syndrome families; patients had impaired T(H)17 cell development, and those with SH2 domain mutations had reduced STAT3 phosphorylation, results suggest that STAT3 is a target of beta-catenin/TCF pathway and might participate in esophageal tumorigenesis, Stat3 is a potent oncogenic molecule that plays a role in formation of lung adenocarcinomas in both mice and humans., The PSMA promoter/enhancer-driven shRNA also depressed the expression of STAT3 in only prostate cancer cells, These findings show a novel mode by which HIF-1alpha is regulated not only in cancer cells but also in the tumor-associated inflammatory cells, suggesting Stat3 as an important molecular target for inhibiting the oncogenic potential of HIF-1., Cucurbitacin B inhibited cell proliferation and induced apoptosis of Hep-2 cells by suppressing the STAT3 signal pathway, and down regulating the expression of cyclin B1 and Bcl-2 proteins., Data show that Stat3 activation and its interaction with Ec-gp96, which in turn interacts with E. coli outer membrane protein A, are critical for E. coli invasion., the loss of PIAS3 in glioblastoma multiforme contributes to enhanced STAT-3 transcriptional activity and subsequent cell proliferation, the Th2 cytokine IL-21 is abnormally expressed in Hodgkin lymphoma cells, which regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3alpha, Significant p-STAT3 expression is associated with colorectal adenocarcinoma., overexpression of p-ATF2, p-STAT3 and possibly p53, but not p63 or p73, may contribute to the tumorigenesis of cutaneous vascular tumors., Wnt (Wnt2), Stat3, and Notch-1 and -2 signaling are correlated in human epidermal tumors., Novel H332Y mutation may result in the loss of function of STAT3 and leads to the hyper-IgE syndrome phenotype., Enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration., Plays a role in the pathogenesis of gestational trophoblastic disease, probably through the regulation of apoptosis., Co-stimulation of G(s) and G(q) can result in the fine-tuning of STAT3 activation status, and this may provide the basis for cell type-specific responses following activation of hIP., Two cases of hyperactivated STAT3 in ALK-positive diffuse large B-cell lymphoma with clathrin-ALK fusion are reported., High expression and activation of STAT3 exist in laryngeal carcinomas., STAT3 expression was significantly related to overall 5-year survival rate in breast cancer patients., This review summarizes the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations [review], STAT3 activation and nuclear accumulation in response to Hepatocyte Growth Factor requires nuclear-proximal activated c-Met., STAT3 NH(2)-terminal domain plays an important role in the interleukin-6 signaling pathway by interacting with the p300 bromodomain, thereby stabilizing enhanceosome assembly., JAK/STAT3 and ERK1/2 signaling activation is involved in leptin-mediated proliferation of renal cell carcinoma Caki-2 cells, Our study suggests a potential role of the STAT3 polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity., green tea extract inhibits angiogenesis partly through the disruption of STAT3-mediated transcription of genes, STAT3 constitutive activation, alone and in concurrence with EGFR expression, plays an important role in high-grade/malignant gliomas and targeting STAT3/JAK2 sensitizes these tumors to anti-EGFR and alkylating agents, S727 phosphorylation is sufficient to activate Stat3, thereby driving prostate tumorigenesis independent of Y705 phosphorylation., STAT3 single-nucleotide polymorphisms and STAT3 mutations associated with hyper-IgE syndrome are not responsible for increased serum IgE serum levels in asthma families, Expression of EBV LMP1 is positively correlated with Fascin, pStat3 and the proliferation index of tumor cells in nasopharyngeal carcinoma., BDNF- and seizure-dependent phosphorylation of STAT3 cause the adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) family member ICER (inducible cAMP early repressor) to bind with phosphorylated CREB at the Gabra1, elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J., combined use of IFN-alpha and IL-21 boosts STAT3 signaling, cytotoxicity, and anti-tumor efficacy, suggesting that a combinatorial therapeutic use of these cytokines may benefit cancer patients., TCPTP is a negative regulator of SFK, JAK1 and STAT3 signalling during the cell cycle., Stat3 played an important role in the G1 to S phase transition in laryngocarcinoma cells., mutations cause autosomal-dominant hyper IgE syndrome; lead to disruption of cytokine signaling pathways, Results suggest that STAT3 decreases the pVHL-mediated ubiquitination of HIF-1alpha through competition with pVHL for binding to HIF-1 alpha, and then stabilizes HIF-1alpha protein levels., IL11 inhibits human extravillous trophoblast invasion via STAT3, indicating a likely role for IL11 in the decidual restraint of EVT invasion during normal pregnancy., These results support the hypothesis that STAT3 and CREB play an important role in leptin signaling pathway that leads to the proliferation of Ishikawa cells, thus establishing a direct association between obesity and endometrial tumorogenesis., S-glutathionylation of STAT3, a modification that may exert regulatory function in STAT3 signaling., data indicate overexpression of mesothelin in pancreatic cancer cells leads to constitutive activation of Stat3, resulting in enhanced expression of cyclin E & cyclin E/cyclin-dependent kinase 2 complex formation & increased G(1)-S transition, STAT3 was expressed at higher levels in patients with diabetic nephropathy than in control subjects., guggulsterone not only induces apoptosis, but also inhibits angiogenesis and metastasis in colon cancer cells by blocking STAT3 and VEGF expression, EBNA2 is a transcriptional coactivator of STAT3 by influencing its DNA-binding activity., FoxO1 binds to STAT3 and prevents STAT3 from interacting with the SP1.POMC promoter complex, and consequently, inhibits STAT3-mediated leptin action., Cell confluency-induced Stat3 activation regulates NHE3 expression by recruiting Sp1 and Sp3 to the proximal NHE3 promoter region during epithelial dome formation., LKB1 protein might inhibit malignant biological behavior of A549 cells partly by down-regulating the tyrosine-phosphorylated level of STAT3 protein., There are associations with JAK2 and STAT3 implicating the role of this signaling pathway in inflammatory bowel disease., Activated STAT3 is a required part of the continuous activation of B3/B4 genes, which protects tumor cells from dying., In primary human leukemia samples, there was a positive correlation between HMGA1a and STAT3 mRNA. Moreover, blocking STAT3 function in human leukemia or lymphoma cells led to decreased cellular motility and foci formation., mutations in the STAT3 gene in most of the patients with type 1 hyper-IgE syndrom (Review), Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1).(, Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas., In this review, studies of STAT3 deficiency in humans highlight nonredundant roles of STAT3 in diverse cellular processes such as antimicrobial immunity and protection at epithelial barriers, and in hyper-IgE syndrome., STAT3 analysis of essential thrombocythemia shows that in about half of patients, STAT3 hyperactivation is independent of JAK2 mutations. The hyperactivation of STAT3 by JAK2 mutations or promoter activation may be a critical step in development of ET., These results indicate that HDAC3 may act as a scaffold protein for PP2A to regulate the LIF/STAT3-mediated signaling pathway., STAT pathways and survivin could be potential targets for reducing resistance developed in patients receiving FLT3 inhibitors, Boswellic acid is a novel inhibitor of STAT3 activation and has potential in the treatment of cancer., Interaction between STAT3 and Fer was observed in all prostate cancer cell lines tested, and this interaction is modulated by interleukin-6., Results indicate that H. pylori CagA activates the STAT3 signaling pathway in vitro and in vivo, providing a potential mechanism by which chronic H. pylori infection promotes the development of gastric cancer., there was a statistically significant dependence of the EGFR status on STAT3 expression in neoplastic tissues, Site-directed mutagenesis of all four putative STAT3-binding sites in the SALL4 promoter significantly reduced its responsiveness to STAT3, although the most dramatic effect was seen at the binding site starting at -199., G-Gly inhibits apoptosis in Barrett's oesophagus and oesophageal adenocarcinoma via mechanisms distinct from those activated by G-17 and involving JAK2 and STAT3 activation., Antisense oligodeoxynucleotides that inhibited Stat3 could induce apoptosis and suppress cell proliferation in laryngeal carcinoma Hep-2 cells., STAT3 expression in gastric cancer indicates a poor prognosis., BITC (benzyl isothiocyanata) induces apoptosis in some types of pancreatic cancer cells by inhibiting the STAT-3 signaling pathway., STAT3 transactivates its target genes by the recruitment of CBP/p300 co-activators and this process generally does not require the contribution of SRC-1., Sustained Src inhibition results in signal transducer and activator of transcription 3 (STAT3) activation and cancer cell survival via altered Janus-activated kinase-STAT3 binding., IL-7 stimulates chondrocyte secretion of S100A4 via activation of JAK/STAT signaling, and then S100A4 acts in an autocrine manner to stimulate MMP-13 production via RAGE., STAT3 physically interacts with stathmin to regulate microtubule dynamics in migrating T-cells., These results indicate that MAGOH regulates the transcriptional activation of STAT3 by interfering complex formation between STAT3 and Y14., Data show that the mechanism of G-CSF-induced chemotaxis appears to involve the phosphorylation of JAK1/STAT3 pathway., IL-12 stimulates the OIP-1 gene expression through STAT-3 activation in CD4+ T cells, STAT3 mediates negative regulation of hepatic gluconeogenic gene expression in vivo by interacting with regulatory regions of these genes., STAT3 activation is critical in IL-17A-mediated CC chemokine ligand 11 (CCL11) expression in human airway smooth muscle cells., Data indicate an almost universal expression of activated Stat3 in benign and malignant salivary gland tumors., experiments demonstrate that Stat3 has both - tumor suppressing and tumor promoting properties, -ATF2 and p-STAT3 are concordantly overexpressed in extramammary Paget's disease and their expressions may possibly be associated with the tumor stage., Data suggest that STAT3 activation contributes to the survival and proliferation of OSA cells, thereby providing a potentially promising target for therapeutic intervention., This study indicates that phosphatidic acid acts as an important mediator for increasing Bcl-2 expression through STAT3 (Ser727) activation via the ERK1/2 MAPK pathway., Role of RAF/MEK/ERK pathway, p-STAT-3 and Mcl-1 in sorafenib activity in human pancreatic cancer cell lines., Diesel particle-induced transcriptional expression of p21 involves activation of EGFR, Src, and Stat3, mTOR signaling is one major mechanism in a tightly regulated network of intracellular signal pathways including the JAK/STAT system to regulate invasion in human trophoblast cells by secretion of enzymes that remodel the extra-cellular matrix., Data suggest that colorectal neoplasms are STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis., Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors., A novel mutation in the linker domain of the signal transducer and activator of transcription 3 gene, p.Lys531Glu, in hyper-IgE syndrome., Targeting Stat3 signaling using siRNA may serve as a novel therapeutic strategy for the treatment of breast cancers expressing constitutively activated Stat3., Focusing on how STAT3 work in concert with other transcription factors will hopefully provide a better mechanistic understanding of the pathogenesis of various autoimmune diseases., persistent activation and nuclear translocation but not upregulation of STAT3 occurs in ALS spinal cord microglia., The JAK3/ERK pathway may play an important role in epidermal growth factor induced MMP-9 expression in SKBR3 cells., Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway., STAP-2 is phosphorylated at Tyr250 by Brk, and plays an important role in Brk-mediated STAT3 activation., There was a significant correlation between the expression of p-STAT3 and that of osteopontin in melanoma., EGFR, NFkappaB, and STAT3 are required for human iNOS gene induction in proximal tubule cells in response to pressure or EGF, indicating a similar mechanism of activation., activated STAT3 is highly present in glioma but not normal brain tissues, STAT3 protein has a major role in the oncogenic process of nasal-type NK-cell lymphomas, and may represent a promising therapeutical target., interactive effect between HPV 16/18 and transcriptional activation of STAT3 gene in cervical carcinogenesis, STAT3 is frequently found to be constitutively active in breast cancer and tumors can become addicted to STAT3. Review., These findings suggest that kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway., Data show that ARHI could compete for Ran-importin binding and induce disruption of importin-binding to cargo proteins, including STAT3., GATA-1 can reverse STAT3-mediated gamma-globin gene silencing in erythroid cells, Apoptotic body engulfment by hepatic stellate cells promotes their survival by the JAK/STAT and Akt/NF-kappaB-dependent pathways., Data show that blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively., Using a model system of paired breast cancer cell lines, we found that coactivation of STAT5 and STAT3 leads to decreased proliferation and increased sensitivity to the paclitaxel and vinorelbine compared with cells that have only STAT3 activation., The EGF/PI3K/STAT3 signaling is identified as an essential pathway regulating VEGF and leptin expression in EGF-responsive colon cancer cells., Data show thatCypA and CypB both play pivotal roles, yet at different signaling levels, for Stat3 activation and function., Data show that in the nucleus, the acetylated STAT3 dimer is associated with CD44 and binds to the cyclin D1 promoter, leading to increased cyclin D1 expression and cell proliferation., Stat3 is an essential signaling component potentially contributing to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia caused by PTPN11 gain-of-function mutations, malignant transformation by activated Ras is impaired without STAT3; STAT3 was detected in mitochondria; findings show STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation, findings suggest that Stat3 and p53 are cooperatively involved in the development of renal cell carcinoma (RCC) but assessment of their mRNA expression may not be useful for predicting the prognosis of patients with RCC, mechanisms underlying different forms of hyper IgE syndrome and their functional outcome by investigating the incidence of STAT3 mutations and the competency of TH17 cell differentiation in a cohort of affected Turkish children were elucidated., constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo., These results suggest that IkappaB-zeta is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-kappaB signaling pathway inhibits the activation of STAT3., Studies indicate that STAT3 plays dual tumor suppressive and oncogenic roles in glial malignancy depending on the mutational profile of the tumor., Findings suggest that STAT3 might be an excellent target for therapeutic intervention in tumor metastases., Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation., Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-kappaB, and STAT3 signaling pathways., these findings support the enhancement of JAK3/STAT3 activation and cell growth in anaplastic lymphoma kinase positive - anaplastic large cell lymphoma via IL-21 signaling., A431 cells (human squamous cell carcinoma cells with EGFr overexpression) were found to be sensitized to radiation after treatment with STAT-3 small interfering RNA (siRNA)., study concludes that Stat3 controls a specific gene set in trophoblast-like JEG-3 cells, hypoxia-induced STAT3 activation is responsible for chemoresistance., IL-6, but not IFN-gamma, could significantly impair the in vivo growth of STAT3-depleted human neoplastic T lymphocytes, Data show that deletion of the C-terminal part of IL-22R dramatically decreased its ability to activate STAT3., p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis., Data show that restoration of GRIM-19 levels reestablishes the control over STAT3-dependent gene expression and tumor growth in vivo., STAT3 has a critical role in regulating ovarian cancer cell motility and this process can be prevented by curcumin., Cholestasis or its important component-hydrophobic bile acids-can downregulate hepcidin expression through inhibiting IL-6-induced STAT3 phosphorylation and pSTAT3 protein nuclear translocation., TYK2 and STAT3 are genetic determinants of Crohn's disease in the Japanese population., These data suggest that STAT3 regulates the growth and self-renewal of GBM-SCs and is thus a potential target for cancer stem cell-directed therapy of glioblastoma multiforme., pSTAT3tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer, Studies indicate that a better understanding of the mechanisms of dysregulation of the STAT pathway and leukemogenesis may serve as a basis for designing novel therapeutic strategies directed against STATs., This study not only reveals a role of CRT in motility promotion and anoikis resistance in ESCC cells, but also identifies CRT as an upstream regulator in the CRT-STAT3-CTTN-Akt pathway., chronic inflammatory demyelinating polyradiculoneuropathy(CDIP)patients with active disease showed higher pSTAT1, T-bet, & pSTAT3 in CD4(+) T-cells & monocytes than controls, Studies have demonstrated that mutations in STAT3 and TYK2 genes result in Hyper-IgE syndrome (HIES., data suggests that, in at least certain cellular microenvironments, cell, aStudies indicate that the phosphorylation of STAT-3 at serine 727 may regulate its activity negatively or positively., Curcumin analogue GO-Y030 inhibits STAT3 activity and cell growth in breast and pancreatic carcinomas., we have identified a novel regulatory pathway involving increased gene expression of the SNAT2 isoform mediated by a STAT-dependent pathway, which links IL-6 to increased activity of amino acid transporter system A, cholinergic agonists suppress IL-6-mediated endothelial cell activation through the JAK2/STAT3 pathway, Visfatin through STAT3 activation enhances IL-6 expression that promotes endothelial angiogenesis., The upregulation of IL-8 production is caused by constitutive STAT3 activation at the level of gene transcription in melanoma cells., Tensile stress can activate the expression of p-ERK and p-STAT3 in alveolar epithelium A549 cells., STAT3 played an important role in the response and signal transduction of bronchial epithelial cells to the cyclic mechanical stretch stimulation through the phosphorylation of STAT3 Tyr705., STAT3 gene polymorphisms influences the risk of abdominal obesity, which is modulated by dietary saturated fat inttake., deguelin presents a potent anti-proliferative effect in part via the down-regulation of survivin expression and STAT3 phosphorylation in HTLV-1-transformed cells., Molecular dynamics simulations were performed in explicit water of the activated Stat3 homodimer, and also its closely related member of the STAT family, activated Stat1 homodimer., ATRA blocks Squamous cell carcinoma (SCC) of the skin tumor formation, at least in part, by targeting events upstream of Stat3, The Stat3/5-dependent activation of cytokine expression in osteoblasts may have a significant impact on cancer cell migration and proliferation, but also on osteoclast activation., STAT3 is a weak anti-apoptotic agent, Studies suggest that a STAT3-SCLIP interaction is required to preserve SCLIP stability and contributes to the maintenance of normal epithelial morphology., Taken together, these data show that mt p53 (G199V) gains antiapoptotic function mediated by STAT3 in ATC cells., tumor-associated STAT3 is silenced by an oncolytic adenovirus, STAT3 has this dual role in tumour inflammation and immunity by promoting pro-oncogenic inflammatory pathways., analysis of reciprocal regulation of c-Src and STAT3 in non-small cell lung cancer, STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling., detected ERalpha binding to STAT3 and JAK2 (Janus kinase 2), resulting in enhanced JAK2 activity upstream of STAT3 in response to leptin that might lead to an increased ERalpha-dependent cell viability, baicalein not only inhibited IL-6-mediated phosphorylation of signaling proteins, such as Jak, STAT3, MAPK, and Akt, but also inhibited the expression of their target genes, such as bcl-xl., Elevated levels of STAT3 protein are characteristic of Burkitt lymphoma cells refractory sto EBV lytic cycle induction by HDAC inhibitors., Data suggest that the percentage of peripheral blood mononuclear cells displaying p-STAT-3 may be increased in malignant glioma patients., A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3., Studies indicate that signaling pathways of STAT3, NOTCH, hedgehog and transforming growth factor-beta (TGFbeta), which are involved in stem cell renewal, differentiation, survival, and are commonly deregulated in HCC., data suggest an important role for the negative regulatory effect of PIAS3 on STAT3 in EGF-driven tumors, the human SREBP-1c promoter was positively regulated by insulin and negatively regulated by STAT3., This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-kappaB, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients., The downregulation of miR-21 contributes to the antitumor effects of IFN-beta and that miR-21 expression is negatively regulated by STAT3 activation., findings suggest that overexpression of p-STAT3 (Tyr705) occurs in urothelial carcinoma, and that pathways other than SOCS3 may contribute to its activation in this cancer, STAT3 activation is associated with Mcl-1 expression in nasal NK-cell lymphoma, ERp57 is a necessary cofactor for the regulation of at least a subset of STAT3-dependent genes., the activation of JAK/STAT3 pathway by GHRH, The STAT3 signal pathway regulates cell proliferation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma cells., study indicates that IL-6 induces a novel STAT3-APE1 complex, whose interaction is required for stable chromatin association in the IL-6-induced hepatic acute phase response, these findings uncover a novel mechanism whereby IL-10-activated STAT3 modulates IL-1ra transcription in LPS-treated phagocytes by making IL-1ra promoter accessible to readily available nuclear NF-kappaB., In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome, Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade., Specific siRNA targeting STAT3 gene is able to enhance the radiosensitivity in Hep-2 cells by regulating expression of Bcl-2, VEGF and p53 proteins., STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients., The STAT3 has an important role in the occurrence and development of human meningioma by regulating VEGF expression., Expression of a constitutively activated STAT3 mutant or myristoylated AKT partially blocked the effects of sunitinib in these tumor cells., These findings indicate that cancer-initiating cells contribute to the immune evasion of glioblastoma multiforme and that blockade of the STAT3 pathway has therapeutic potential., Levels of STAT3 mRNA correlate with polymorphic differences in genes encoding interferon alpha signal transduction components and might account for different patient responses in chronic myeloid leukemia., Plumbagin inhibits STAT3 activation pathway through the induction of SHP-1 and this may mediate the sensitization of STAT3 overexpressing cancers to chemotherapeutic agents., These results indicate that Stat3 plays a key role in the invasion and apoptosis of human glioma cell line U251., Data suggest that INCB16562 is a potent JAK1/2 inhibitor and that mitigation of JAK/STAT signaling by targeting JAK1 and JAK2 will be beneficial in the treatment of myeloma patients, particularly in combination with other agents., Data show that LLL12 inhibited STAT3 phosphorylation, induced apoptosis as indicated by the increases of cleaved caspase-3 and poly (ADP-ribose) polymerase, and also downregulated cyclin D1, Bcl-2, and survivin at both protein and messenger RNA levels., Stat3 could be the major target for increasing chemosensitivity in patients who develop chemoresistance during chemotherapy., Human placental multipotent mesenchymal stromal cell-conditioned medium activated STAT3 expression in endothelial cells, supporting cell survival. STAT3 activation and SOD2 production protect against oxidative stress-induced endothelial cell damage., Carrying either the JAK2 or STAT3 IBD risk allele was associated with significantly enhanced susceptibility to DNA damage, as estimated by comet assays, lack of spontaneous STAT3 and STAT5 activation and the normal response to TPO is unexpected as MPLW515L leads to constitutive receptor activation and hypersensitivity to TPO in experimental models, The mRNA expression levels of EGFR and STAT3 in laryngeal papilloma tissue were significantly higher than that in normal laryngeal tissue. p-STAT3 expression was correlated with recurrence and metastasis., A chemical genetics approach reveals STAT3 as a novel neurofibromin/mTOR pathway signaling molecule, define its action and regulation, and establish STAT3 as a tractable target for future NF1-associated cancer therapy studies., Data suggest that the up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis, demonstrates that antiphospholipid antibodies limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity., These findings indicate the existence of the nuclear EGFR/EGFRvIII signaling pathway in GBM and its functional interaction with STAT3 to activate COX-2 gene expression., constitutive activation of Stat3 signaling pathway may play an important role in the invasion and prognosis of epithelial ovarian carcinoma., data suggest that the novel G342D mutation affects the binding of STAT3 on DNA and the STAT3-dependent expression of retinoid-related orphan receptor gammat mRNA, leading to the hyper-IgE syndrome phenotype., constitutive phosphorylation of STAT3 on serine 727 residues is a hallmark of CLL and that STAT3 be considered a therapeutic target in this disease., STAT3 represents a shared risk locus for multiple sclerosis and Crohn disease., p-STAT3 levels are decreased in chronic rhinosinusitis with nasal polyps despite increased levels of IL-6 and sIL-6R and are associated with the absence of an IL-17 response, In 64 patients with hyper-IgE syndrome, we identified 31 different STAT3 mutations, 18 of which were novel., ZIP4 overexpression causes increased IL-6 transcription through CREB, which in turn activates STAT3 and leads to increased cyclin D1 expression, Expressions of STAT3 show mutual correlations in primary ductal breast cancers, which suggest co-operation among the protein., Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth, 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling, Targeting STAT3 may enhance treatment efficacy against pancreatic cancer., Treatment of a glioblastoma stem cell line culture with a STAT3 phosphorylation inhibitor (WP1193) or 10% FBS (fetal bovine serum) both led to a decrease in expression of the stem cell marker CD133, but differed in phenotype changes., Data show that the STAT3 haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD., STAT3 inhibition using si-RNA suppressed VEGF secretion in the SNU-1041 head and neck cancer cell line, STAT3 has a role in in vitro transformation triggered by TRK oncogenes, STAT3 inhibition downregulated the expression of Bcl2 family of anti-apoptotic gene Bcl-xL., IL-6/STAT3/TFF3 signaling is involved in human biliary epithelial cell migration and wound healing., VEGF expression in breast cancer cells is mediated by HIF-1 and STAT3 in a miR-20b-dependent manner., IR induces Bcl-X(L) accumulation via STAT3, which then promotes cancer cell invasion and epithelial-mesenchymal transition(EMT)-associated markers., the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling., Treatment of lymphocytic choriomeningitis virus Armstrong-infected Stat3 conditional knockout mice induces neither immune suppression or T cell deletion., the immunosuppressive effects of IL-10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expres, Stat3 and Cyclin D1 were overexpressed in laryngeal neoplasm tissue, and they have a positive relationship., Over-expression of JAK/STAT signal pathway may be an important feature of hepatocellular carcinoma., High nuclear STAT3 expression levels are not associated with head and neck squamous cell cancers., amplified FGFR expression engages the STAT3 pathway, Stat3 activation is induced by hydrogen peroxide exposure to the skin in healthy individuals, JAK2/STAT3/vimentin signaling pathway participates in regulating the proliferation and migration of human colon cancer cells., Src kinase-mediated activation of STAT3 and subsequent angiogenic gene expression mediate the effects of integrin alpha v beta 5 and may be exploited to enhance the paracrine activities of circulating angiogenic cells., we studied the immunohistochemical expression of STAT-3 proteins in primary central nervous system lymphomas, HBx-mediated down-regulation of let-7a and up-regulation of STAT3 supports cell proliferation in HBx cells., Stat3 activation in UV-exposed skin is one of the initial events where DNA damage and ROS are involved., Stat3 pathway is overexpressed in multidrug resistant osteosarcoma cells. CDDO-Me significantly inhibited Stat3 phosphorylation, Stat3 nuclear translocation and induced apoptosis in osteosarcoma., These data identify atypical PKC isozymes as STAT and ERK activators that mediate c-fos and collagenase expression., IL-22, likely via activation of STAT3 and downstream genes (e.g., SOCS3), is able to protect against cell stretch and pulmonary baro-/biotrauma by enhancing epithelial cell resistibility, High STAT3 is associated with the maintenance of neurosphere-initiating tumor cells in patients with glioblastomas., Thymic stromal lymphopoietin induced proinflammatory gene expression in human airway smooth muscle cells involved ERK1/2, p38, and JNK, and STAT3 activation., Interferon-gamma-induced suppressor of cytokine signaling (SOCS)3 expression leads to inhibition of interleukin (IL)-6-induced STAT3 activation and IL-6-dependent expression of anti-, but not pro-inflammatory, target genes., genetic polymorphism is associate with Hyper-IgE syndrom (case report from Cina), significantly decreased cell viability and increased apoptosis in human neuroblastoma cell line in association with down-regulation of p-ERK1/2, p-Akt, p-STAT3 survival pathways., arecoline induces anoikis of HA22T/VGH cells involving inhibition of STAT3 and increased RhoA/Rock activation, STAT3 is an important target for human GSCs in regulation of glioblastoma stem cells(GSCs) growth, apoptosis, differentiation and tumorigenic potential., The proportion of phosphorylated STAT3alpha relative to STAT3alpha was significantly greater in supratentorial PNETs than in medulloblastomas., the cdk5-STAT3 oncogenic pathway plays an important role in the expression of DNA repair genes and that these proteins could be used as predictive markers of tumors that will fail to respond to chemotherapy., These findings indicate that TRIM8 enhances the STAT3-dependent signal pathway by inhibiting the function of PIAS3., Interleukin-27 induces a STAT1/3- and NF-kappaB-dependent proinflammatory cytokine profile in human monocytes, STAT3 plays crucial roles in osteosarcoma development, simultaneous expression of HGF/c-met and three trasducers of tyrosine kinase receptors STAT3, PI3K, RHO in both nodular and extranodular tissues were studied by immunohistochemistry in 50 benign thyroid nodules, 25 associated with Hashimoto's thyroiditis, LLL12, a STAT3 small molecule inhibitor, blocked IL-6-induced STAT3 phosphorylation, resulting in attenuation of the anti-apoptotic activity of IL-6., HIV-1 activation of STAT1 and STAT3 in human brain microvascular endothelial cells (HBMEC) is associated with induction of promoter activity of the interferon-stimulated response element (ISRE)/interferon-gamma-activated sequence (GAS)., Impaired downregulation of gp130-mediated STAT3 activation in subacute infarction promotes cardiac inflammation, adverse remodeling, and heart failure, suggesting a potential causative role of high interleukin-6 serum levels after myocardial infarction., There was no difference in the distribution of allele and genotype in either JAK2 or STAT3 between ankylosing spondylitis groups and controls., AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3)., STAT3 was activated in primary mantle cell lymphoma cells either constitutively through a cytokine autocrine loop or in response to B-cell receptor engagement, both processes leading to a survival signal inhibited by bortezomib., Data show that STAT3alpha may therefore be a common mediator of oncogenic signaling pathways stimulating progression of EC., Data suggest that constitutively activated Stat3 binds to the ROR1 promoter and activates ROR1 in CLL cells., Data demonstrate that eradication of signal transducers and activators of transcription (STAT3) signaling considerably enhances BMP-induced osteogenic differentiation of hMSCs, Our study provides evidence that the up-regulation of STAT-3 in colonic mucosa may be associated with the progression of ulcerative colitis., STAT3 is not only a downstream target of IL-6 but, with miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer., Expression of a redox-insensitive STAT3 in breast carcinoma cells accelerates proliferation while reducing resistance to oxidative stress., Data identified the oncogenic transcription factor STAT3 as a binding partner of nuclear survivin., our results support the concept that STAT3 upregulates the protein expression and transcriptional activity of beta-catenin in breast cancer, Cell-cell contacts induce STAT3 activity in colon carcinoma cells through an autocrine stimulation loop., Stat3 activation by IL-6 and IL-10 plays an important role in cell-to-cell interaction between tumor cells and macrophages in the ascites of advanced epithelial ovarian cancer (AdEOC)., NF-kappaB and STAT3 transcription factors are especially important signaling hubs for integrating signal pathways to orchestrate effective host defense without excessive inflammatory injury., STAT3 was positively correlated with the neovascularization of nasal polyps, and was also positively correlated with VEGF expression., The expression of STAT3 and c-myc may play an important role in the tumorigenesis, metastases and poor prognosis of laryngeal squamous cell carcinoma., Abundant tyrosine phosphorylation of STAT3 leads to primary resistance to EGFR inhibitors in lung cancer., STAT3 activation mediates, at least in part, IFN-gamma-induced neurotoxicity and ICAM-1 expression by human astrocytes., Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells., Activated STAT3 directly bound to IL6 promoter and increased IL6 mRNA and protein secretion., STAT3 and c-Jun could physically interact and bind to the AP-1 site, implicating that the interplay of both transcriptional factors on the AP-1 site is responsible for isoproterenol-stimulated MMP-7 expression in gastric cancer cells., Lower expression of SSTR2 and activation of STAT3 in olfactory neuroblastoma cells might contribute to the development of ONB., A role was determined for signal transducer and activator of transcription 3 and Janus kinase-2 transduction in alpha4beta2 nicotinic receptor-mediated anti-inflammatory effects., We validated STAT3 as a bona fide target of BCL3 in a cervical cancer cell line by additional interference RNA and in silico analyses of previously reported lymphoma patients., Data show that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV16-mediated cervical carcinogenesis., Adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6, by downregulating STAT3 phosphorylation., Autosomal dominant hyper-IgE syndrome (AD-HIES), characterised by eczema, increased susceptibility to skin and lung infections, elevated IgE and skeletal abnormalities is associated with heterozygous STAT3 mutations., results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with ankylosing spondylitis in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations., Data show that STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells., MicroRNA-21 expression in CD4+ T cells is regulated by STAT3 and is pathologically involved in Sezary syndrome., Data show that STAT3 binds to the SOCS3 promoter, and S727 is then phosphorylated, followed by the coincident binding of SET9 and dimethylation of K140, and lastly by the binding of LSD1., STAT3-dependent IL-22 signaling and effects in keratinocytes are negatively regulated by SIRT1, all of the phosphorylated STAT3 positive cells were also positive for phosphorylated STAT1, both of which could be inhibited by a JAK2/STAT inhibitor, AG490, Findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance., butein exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo, a negativie correlation between the expressions of STAT3 and WWOX, but no relationship was found between WWOX and c-myc, Activation of the IL-6/STAT3 pathway in transformed Barrett's epithelial cells enables them to resist apoptosis, indicating a possible contribution of the intrinsic inflammatory pathway to carcinogenesis in Barrett's esophagus., Hyperresponsiveness of transgenic glycoprotein (gp)130 mice to lipopolysaccharide involves specific upregulation of IL-6 in a gp130/STAT3- and Toll-like receptor 4/MyD88-dependent manner., Chr1q32 and STAT3 are ankylosing spondylitis susceptibility loci., STAT3-mediated leptin receptor signaling pathways may be activated in human colorectal adenomas., Inactivation of STAT3 in pancreatic cancer cell lines induces apoptosis but also may promote the expression of anti-apoptotic genes., NZB treatment determines an accumulation of CD4+T-bet+, CD4+pSTAT3+ and CD8+T-bet+ T cells in the peripheral blood of natalizumab treated multiple sclerosis patients., Mutations of STAT3 and clinical manifestations of hyper IgE syndromes (Review), Results reveal an elegant mechanism of eNOS regulation by PECAM-1 through signal transducers and activators of transcription 3-mediated transcriptional control of NOSTRIN., Authors believe in order to exclude the association of STAT3 polymorphisms with MS in particular and any other autoimmune disorders in general, we should investigate polymorphisms in more than four regions within the gene., Siltuximab effectively blocks the IL-6/Stat3 signaling pathway in ovarian cancer., Loss of STAT3 activity in lung cancer cells resulted in reduced cell proliferation and apoptosis and combined EGFR and STAT3 loss had additional antitumor effects., The CRE-like site located near the SBE may contribute to the formation of a stable complex of STAT3, HIF-1alpha, and p300/CBP, which leads to maximum transcription of the Hp gene., CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is down-regulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level, our findings reveal a novel role for STAT3 in NK cell immunosurveillance by modulating the MICA expression in cancer cells., During dendritic cell differentiation toll-like receptor agonists induce a STAT-3-mediated expression of PD-L1 and favor the development of tolerogenic antigen presenting cells., Extracellular hepatitis C virus core protein activates STAT3 in human monocytes/macrophages/dendritic cells via an IL-6 autocrine pathway., The effects of the site of mutation in the STAT3 domains that are associated with autosomal dominant hyper IgE syndrome are reported., Interleukin-6 induction of toll-like receptor 4 gene expression via signal transducer and activator of transcription 3(STAT3) is one of the main mechanisms underlying insulin resistance in human skeletal muscle, Strong activation of Stat3, such as by interleukin (IL)-6 in inflamed tissue, results in release from regulatory T cell suppression, whereas functional suppression is restored upon concurrent activation of Stat1., Common variation in the STAT3 may influence mtDNA copy number., STAT3 activation in colorectal cancer is associated with adverse clinical outcome, STAT3 down-regulation resulted in an increase of Survivin/BIRC5 and BCL-xL mRNA in pancreatic neoplasms., activated STAT3 signal may associate with Twist and E-cadherin expression and mediate HCC invasiveness and metastasis., STAT3 phosphorylation is increased in skeletal muscle following intense exercise., Data show that MUC1-C interacts directly with JAK1 and STAT3., mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer, ATP-binding membrane cassette transporter A1 and signal transducer and activator of transcription 3 have roles in tristetraprolin-dependent post-transcriptional regulation of inflammatory cytokine mRNA expression by apolipoprotein A-I, Data supports activation of a central IL6-STAT3-HIF1A pathway in OCCA., malignant T cells in cutaneous T-cell lymphoma (CTCL) lesions express IL-17 and that this expression is promoted by the Jak3/Stat3 pathway., STAT-3 binds to the NF-kappaB p50/p65 dimers and that the STAT-3/NF-kappaB complexes bind to DNA and activate NF-kappaB-regulated genes, inhibition of the inappropriate activation of STAT3/Pim1 axis is a novel, specific, and attractive therapeutic strategy to reverse Pulmonary artery hypertension., Signal transducer and activator of transcription 3 (STAT3) and Suppressor of Cytokine Signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in decidual-like natural killer cell line NK-92., Data show that PrLZ elevated the phosphorylation of Akt and Stat3 and upregulated Bcl-2 expression., Data show that CD5 expression is associated with NFAT2 activity and mildly STAT3 activity, indicating that CD5 controls IL-10 secretion., The purpose of this study was to investigate the possible suppressive or stimulatory role of OSM in the ovarian cancer model of SKOV3 cells, as well as the involvement of the ERK1/2, p38 and STAT3 signaling pathways., CYP3A4 is a highly active AA epoxygenase that promotes Stat3-mediated breast cancer cell growth in part through (+/-)-14,15-EET biosynthesis., IL-6 induction of STAT3 signaling occurred exclusively in the nuclei of satellite cells in response to muscle-lengthening contractions., Finding supports the notion that the combination of inappropriate STAT3 and AP-1 activities drives elevated MMP-1 expression and tissue invasion in colorectal cancer., Data show that ALK inhibitor-induced apoptosis is mediated both by BIM upregulation resulting from inhibition of ERK signaling as well as by survivin downregulation resulting from inhibition of STAT3 signaling in EML4-ALK-positive lung cancer cells., The JAK2/STAT3 signaling pathway plays an important role in the angiogenesis of non-small cell lung cancer., JAK1/STAT3 signaling mediates CK-induced apoptosis in U266 cells and also suggest the chemopreventive potential of CK for treatment of multiple myeloma., First report of type I hyper-IgE syndrome (HIES) showing a STAT3 gene mutation and MCNS., Single nucleotide polymorphisms in STAT3 is associated with prostate cancer., STAT3 phosphorylation is an early event in the healing response to muscle injury after repeated biopsy, probably mediated by the autocrine production of IL-6., There was a positive correlation between STAT3 and vimentin expression and a negative correlation between STAT3 and E-cadherin in colon cancer., The novel curcumin analog FLLL32 has biologic activity against osteosarcoma cell lines through inhibition of STAT3 function and expression., STAT3 mediates resistance to MEK inhibitor through microRNA miR-17, STAT3 enhances the proliferation of limbal keratinocytes through a DeltaNp63-dependent mechanism. Suppression of this pathway inhibits cell proliferation with a concomitant increase of cell differentiation., Intracellular apoptotic signals in HHUA cells are constitutively activated and regulated by STAT3-mediated signals., Activation of a pro-survival IL-6/JAK2/STAT3 cascade contributes to cholera toxin-induced GFAP expression., STAT3 signaling pathway plays an important role in the angiogenesis of pancreatic cancer., show that Stat3 signaling enforces MMP7 expression in pancreatic ductal adenocarcinoma cells and that MMP7 deletion limits tumor size and metastasis in mice, data describe the involvement of IL-6 transsignaling/Stat3/Socs3 in pancreatic intraepithelial neoplasia progression and pancreatic ductal adenocarcinoma development, Constitutively active STAT3 rescued the effects of BMX downregulation, supporting that BMX signals through STAT3 in glioblastoma stem cells (GSCs)., Gene silencing of STAT3 leads to cell death by blocking nuclear transfer of STAT3 and STAT3-bound NF-kappaB., chronic lymphocytic leukemic cells express a functional hepatocyte growth factor receptor (c-MET) and hepatocyte growth factor enhanced the viability of these cells through STAT3 phosphorylation, Celecoxib inhibits interleukin-6/interleukin-6 receptor-induced JAK2/STAT3 phosphorylation in human hepatocellular carcinoma cells, STAT3 plays an integral role in human vascular remodeling and atherosclerosis in a Hyper-IgE syndrome (HIES) cohort patients., STAT3 facilitates NF-kappaB binding to genes that are important for tumor growth while inhibiting its binding to Th-1 immunostimulatory genes in growing tumors, including in tumor-infiltrating immune cells., the level of Stat3 Tyr705 phosphorylation was decreased in B7-H3 knockdown cells ., LLL12 significantly inhibited STAT3 phosphorylation., CD109 release from the cell surface in human keratinocytes regulates TGF-beta receptor expression, TGF-beta signalling and STAT3 activation., Activation of the signal transducer and activator of transcription 3 pathway up-regulates estrogen receptor-beta expression in lung adenocarcinoma cells, Our results suggest that the expression of STAT3 might be an independent prognostic marker for NSCLC patients., signaling in liver injury, steatosis, inflammation, regeneration, fibrosis, and hepatocarcinogenesis (review), inhibition of beta-catenin signaling was dependent on its ability to induce DKK1, in a STAT 3-dependent manner. Inhibition of STAT3 and DKK1 abrogated the ability of IFN-gamma to enhance HIV replication in astrocytes., Evidence is presented for the nuclear presence of a functional heteromeric complex of epidermal growth factor (EGFR), Src and the Signal Transducer and Activator of Transcription (Stat)3 proteins in pancreatic cancer cells., constitutive activation of STAT3 is an important factor related to carcinogenesis of human soft tissue tumors and is significantly associated with its clinicopathological parameters, Suggest a potential role for activated pSTAT3 in lymphatic metastases in thyroid cancer., Results show that STAT3 has critical roles throughout the course of PDAC pathogenesis., our findings suggest that SOCS3 inactivation by promoter hypermethylation is mutually exclusive to EGFR activation in gliomas and preferentially promotes glioma cell invasion through STAT3 and FAK activation., Studies indicate that Stat3 signals are pivotal to the proliferation and differentiation of neural stem cells., The regulatory effect of the intronic miRNA on eNOS gene expression was associated with miRNA polymorphisms, and mediated through inhibition of STAT3 signaling in ECs., The data reveal endosomes as central to the genesis, course and outcome of STAT3 signal transduction and transcription., identified a significant association between STAT3 polymorphism and asthma susceptibility in atopic asthma whereas no such association was observed in the non-atopic asthma group, Results indicate STAT3 nuclear import is dependent on the function of importin-beta1, Intratumoral administration of STAT3 transgene-depleted dendritic cells (DC)markedly inhibits colon carcinoma growth of injected and nontreated remote tumors; STAT3-deficient DCs activate T helper (Th)1 cells and resist cancer-derived inhibitory factors., Data show that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts., HIV-1-infected/activated monocyte-derived macrophages induces neural progenitor cell astrogliogenesis through the STAT3 pathway., the loss of ARHI expression in the majority of ovarian cancers may result in the upregulation of Stat3 and FAK activity, and thereby contribute to oncogenesis., The inhibitory effect of RNA interference on STAT3 expression in liver cancer cell line SMMC7721, TRP4 can effectively induce the activation of both NF-kappaB and IL6/STAT3 signaling pathways in the pattern similar to that of classical cytokine, STAT3 and beta-catenin signaling pathway may affect GSK-3beta expression in hepatocellular carcinoma., STAT3 gene polymorphism (rs4769793) was associated with the susceptibility as well as poor differentiation and parametrial invasion of cervical cancer in Chinese women, Leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways., Excessive IL-22 can be found in the hepatocellular carcinoma microenvironment, leading to tumor growth, inhibition of apoptosis, and promotion of metastasis due to STAT3 activation., Data demonstrate a role of STAT3 in regulation of mdr1 gene expression in myeloid leukemia and suggest that STAT3 may be a promising therapeutic target for overcoming MDR resistance in myeloid leukemia., The inhibited viability of HeLa cells caused by knockdown of c-SRC is associated with the decreased content of p-STAT3 protein., In the tumors =2 cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors., The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy., novel Nanog/Stat-3 signaling pathway-specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of HA/CD44-activated HNSCC, study demonstrates that the Src/Stat3 and C/EBP signaling pathways positively regulate the expression of the Jab1 oncogene; results show that Stat3 and LAP2 (C/EBP-beta2) are the two major transcription factors that contribute to Jab1 overexpression that leads to increased proliferation of breast cancer cells, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells., 12% of inflammatory hepatocellular adenoma subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49), We propose that nuclear CD44/acetylated-STAT3 performs an unexpected tumour-progressing function by enhancing cell outgrowth into structures where cells with properties of cancer stem cells can be generated from differentiated somatic cells., CK2 inhibitors enhance the radiosensitivity of human non-small cell lung cancer cells through inhibition of stat3 activation, a novel protective mechanism mediated by mitochondrial STAT3 that is independent of its canonical activity as a nuclear transcription factor., Significant increases in the phosphorylation levels of transcriptional regulation of STAT3-downstream target molecules were observed in colorectal adenoma tissue., immunohistochemical investigation of variables involved in expression of STAT3 (alongside Bak and Bcl-xL) in endometrioid adenocarcinoma tissue, CD24 was found to be a functional liver tumor-initiating cells (T-IC) marker that drives T-IC genesis through STAT3-mediated NANOG regulation., STAT3 is a modifier gene of cystic fibrosis disease., Constitutively activated STAT3 induces vascular endothelial growth factor production by chronic lymphocytic leukemia cells and chronic lymphocytic leukemia cells derive a survival advantage from endothelial cells via cell-to-cell contact., pancreatic Stat3 has a role in ER-mediated suppression of lipid synthesis, JAK2V617F allele burden was higher in polycythemia vera (PV) and primary myelofibrosis (PMF) patients compared with low allele burden in essential thrombocythemia (ET) and early PMF; higher phosphorylation of STAT5 and STAT3 in JAK2V617F positive group, Glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients., Interplay between SIN3A and STAT3 mediates chromatin conformational changes and GFAP expression during cellular differentiation.(, PLTP regulates STAT3 and NFkappaB in differentiated THP1 cells and human monocyte-derived macrophages., Cells transformed by the p110alpha-H1047R mutant of PI3K show increased tyrosine phosphorylation of Stat3., reduced IL-10-mediated phosphorylation of STAT3 in hyper-IgE syndrome patients with mutations in the SH2 domain of STAT3, The data suggested that IL-17A can upregulate keratin-17 expression in keratinocytes in a dose-dependent manner through STAT1- and STAT3-dependent mechanisms., STAT3 is more frequently expressed in non-GCB DLBCL than that in GCB subtype, and its strong nuclear expression is correlated with poor OS in DLBCL., data demonstrate that constitutive activation of STAT3 in Sezary syndrome is not due to the loss of SHP-1, but is mediated by constitutive aberrant activation of JAK family members, results showed a cross-talk between cyclic-AMP and JAK/STAT pathways in liver tumors and they reinforce the role of STAT3 activation in liver tumorigenesis, These results indicate that STAT3 is essential for VEGF-A-induced lymphatic endothelial cell (LEC) migration and tube formation and that STAT3 regulates LEC functions., Epigallocatechin-3-gallate reduces expression of VEGF in gastric cancer cells through the inhibition of Stat3 activity., This is the first evidence that PPAR-gamma activation can counteract STAT-3-dependent escape pathways to IFN-beta-induced growth inhibition through cell cycle perturbation and increased autophagic death in pancreatic cancer cells., The M4 adenovirus could specifically deplete constitutive and inducible STAT3 and phosphorylated STAT3 proteins in ovarian cancer cells., Deregulated expression of pSTAT3 and SOCS3 might possess potential roles in the development and progression of human cutaneous melanoma., Dehydroepiandrosterone reverses pulmonary hypertension in part by inhibiting the Src/STAT3 pathway., STAT3 activities of human papillary thyroid cancer tissues are significantly lower than those of surrounding normal thyroid tissues., ALDH(+)/CD133(+) cells expressed higher levels of the active phosphorylated form of STAT3 than either ALDH(-)/CD133(-) or unfractionated colon cancer cells., Glioblastoma-derived IL-6 is responsible for the observed suppression of Langerhans cell differentiation from CD34(+) precursors but appears to exert this effect in a STAT3 and Raf-1 independent fashion, CD5 costimulation induces more Th17 cells that produce higher amounts of IL-17, which is preceded by prolonged activation of signal transducer and activator of transcription 3 (STAT3)., Both STAT3 and NFkappaB are required for the cytokine-induced expression of fascin in cancer cells., data point toward a pivotal role for an autocrine positive feedback loop involving IL-21 and consequent persistent STAT3 activation in the pathogenesis of Sezary syndrome, both rs6503691 T allele and CT/TT genotypes, but not rs4796793 C/G in STAT3, are associated with a significantly increased risk of dilated cardiomyopathy, polymorphisms in the STAT3 gene may have a protective role in the development of non-small cell lung cancer (NSCLC), particular of stage III/IV NSCLC, NFI-X3 and STAT3 control the migration of differentiating astrocytes as well as migration and invasion of glioma cells via regulating YKL-40 expression., Our results demonstrate that melatonin receptor/Galpha(16) coupling is capable of triggering the production of cytokines including IL-6, and this autocrine loop may account for the subsequent STAT3 phosphorylation at Tyr(705), HDAC1 and HDAC2 differentially modulate STAT activity in response to IFNalpha2, Studies indicate that in Th17 cells, activated STAT3 by IL-6 positively regulates H3K4me3 deposition in the Il17 locus., STAT3 and NF-kappaB pathways co-operate in IgA production, with soluble CD40L rapidly activating the NF-kappaB pathway, probably rendering STAT3 probably more reactive to IL-10 signalling., STAT3 plays an important role in regulation of tumor growth, invasion, and angiogenesis, which could be act by reducing MMP-7 expression in pancreatic cancer cells., IL-6- and TNFalpha-induced TNFR2 expression in colon cancer cells is mediated primarily by STAT3 and provide evidence that TNFR2 may contribute to the tumor-promoting roles of STAT3., a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription., The overall results point towards a novel ability of HDM2 in regulating HIF-1alpha and p-STAT3 levels even in normoxic conditions that eventually lead to an up-regulation of VEGF expression., STAT3 alternative splicing modulation yields an antitumorigenic potential., Phosphorylated Stat3 is associated with neoplastic transformation in patients with colitis., studied the effect of decreased STAT3 signaling on the B-cell compartment in hyper-IGE syndrome with heterozygous STAT3 mutations, STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin., These findings illustrated the biological significance of JAK2/STAT3 signalling in colorectal cancer cell apoptosis., Elp2 and STAT-3 mediate, at least in part, the stimulation of Hsp70 expression by 4PBA., The effects of STAT3 inhibition in colon cancer stem-like cells were examined., A 24h exposure of B lymphocytes with NAC is sufficient to show strong inhibition of STAT3 phosphorylation., pSTAT3 was abnormally expressed in pancreatic adenocarcinoma & related to tumor size, TNM staging & lymphatic metastasis. It may promote tumor angiogenesis via upregulating VEGF & enhance lymphatic metastasis via VEGF-C., a new biological activity for CUEDC2 as the regulator of JAK1/STAT3 signaling and the mechanism by which SOCS3 has been linked to suppression of the JAK/STAT pathway, the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator., This study supports the association between STAT3 and an increase in multiple sclerosis risk., antiproliferative effect of SOCS-1 was attributable not only to the inhibition of STAT3 but also to that of p38 MAPK activity, Enhanced growth inhibition in hepatoma cells treated with both NSC 74859 and cetuximab suggests that cetuximab resistance is probably mediated via STAT3., Constitutive activation of signal transducers and activators of transcription 3 correlates with better prognosis, cell proliferation and hypoxia-inducible factor-1alpha in human gastric cancer., cell-cell interactions of M2 macrophage/microglial cells with lymphoma cells induced Stat3 activation may provide novel insights into PCNSL pathogenesis, Stat3 and its target genes were overactivated and/or overexpressed in drug resistant cells, STAT3 was required for proper induction of IL6 by NF-kappaB, Increased activity of Stat3 and overexpression of PLK1 promote survival and proliferation of esophageal squamous cell carcinoma cells in culture and in mice., A novel dendritic cell(DC) progenitor regulatory pathway in which PGE(2) signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal progenitor survival and differentiation., These data point to a specific role for STAT3 in human central memory T cell formation and in control of certain chronic viruses., Data show that inhibitors of Stat3, IGF-IR and Rho GTPase were the most promising therapeutic agents for ovarian cancer., Acyl derivatives of boswellic acids are inhibitors of NF-kappaB and STATs, STAT3 and STAT5 gene SNPs may be prognostic of leukemia., Activated Stat3 may regulate the migration of breast cancer cells through the regulation of ATX., Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-kappaB and STAT3 pathways., nuclear pSTAT3 might play a role as a tumor suppressor in high-grade salivary gland carcinomas, skeletal myoblasts undergo apoptosis under oxidant stress in a time-dependent manner and preconditioning of skeletal myoblasts significantly prevented their apoptosis via IL-11/STAT3 signaling., Using knockdown of AKT & STAT3, studied the effects of IL-17/AKT signaling in HCC, resulting in IL-6 production, which in turn activated JAK2/STAT3 signaling and subsequently up-regulated its downstream targets IL-8, MMP2, and VEGF., Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders., Data show that ectopic expression of STAT3 abolished the apoptotic effect of dovitinib, indicating that STAT3 is indispensable in mediating the effect of dovitinib in hepatocellular carcinoma (HCC)., TGF-beta1, IFN-gamma, IL-6, and IL-22 induce podoplanin-expression in keratinocytes via STAT3 pathway., STAT3 activation is critical for Varicella-zoster virus replication via a survivin-dependent mechanism., tumor cell-derived IL-6 induced gp130 and IL-6R-dependent activation of STAT3, leading to reduced caspase-3 activation and apoptosis., Heparanase enhances the phosphorylation of STAT3 and STAT5b but not STAT5a in head and neck cancers., STAT3 ''A'' risk allele is associated with increased cellular STAT3 activation and upregulation of pathways that promote recruitment of CXCR2+ neutrophils to the gut., Data suggest that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor., STAT3 genetic polymorphism is associated with the susceptibility to BD., the roles of STAT3 in colorectal cancer epithelial-mesenchymal transition and in STAT3-induced down-regulation of E-cadherin, Taken together our studies further reveal that STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells., Our results suggest that p-STAT3 is an important factor during carcinogenesis and metastasis of lung carcinoma., Persistent activation of STAT3 is a unifying hallmark of a majority of solid malignancies--[REVIEW}, Pien Tze Huang promotes cancer cell apoptosis and inhibition of proliferation via suppression of STAT3 pathway in colorectal neoplasms., peripheral blood lymphocytes (PBLs) of ovarian cancer patients showed lower JAK3, CD3-zeta molecules expression levels, as well as lower STAT3 and CD3-zeta phosphorylation levels than cells of control., phospho-Ser727 determines the duration of STAT3 activity largely through TC45., STAT3-mediated IL-21 signaling can supplement partial t-cell receptor signaling caused by the lack of CD8 association., these results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development., The high expression level of Stat3 and Cyclin D1 protein in laryngeal squamous cell carcinoma was correlated with the clinical stage, tumor differentiation and lymph node metastases., Data indicate that the rs744166 STAT3 variant in homozygous form showed a significantly elevated odds ratio of 1.483 for the development of ulcerative colitis (UC) but conferred no significant risk of Crohn's disease (CD)., Data show that IL-6 treatment increased expression of phosphorylation of signal transducer and activator of transcription 3 (STAT3) and Pim-1 kinase., Findings show that multiple signaling events impinge on Stat3 and that 14-3-3zeta serves as an essential coordinator for different pathways to regulate Stat3 activation and function in multiple myeloma cells., Increased STAT3 and decreased cyclin D1 protein levels may contribute to the recurrence of astrocytic tumours., Increased Phospho STAT3 is associated with progression of esophageal squamous cell carcinoma., The specific knockdown of Stat3 by RNA interference strongly inhibited the motile and invasion activity of tumour cells., Piwil2 plays a role in anti-apoptosis in tumor cells possessing P53 as a positive regulator of STAT3 signaling pathway., SOCS-3 gene induction requires c-Jun, signal transducer and activator of transcription 3, and specificity protein 3 transcription factors., a model of CagA-directed REG3gamma expression in gastric epithelial cells via activation of the IL-11/gp130/STAT3 pathway, Thymic stromal lymphopoietin may upregulate c-Myc expression through activation of STAT3 pathway, thereby inducing trophoblast proliferation., JAK2/STAT3 signaling operates independent of known driver mutations in non-small cell lung carcinoma and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations., This data suggest that STAT3 activation regulates several pathways in human lung fibroblasts associated with normal wound healing, whereas aberrant STAT3 signaling plays a critical role in idiopathic pulmonary fibrosis pathogenesis., The STAT3 pathway plays a key role in mediating CSC properties in ATC-CD133+ cells., IKBKE is a direct target of STAT3 and is induced by tobacco carcinogens through STAT3 pathway., A subset of genes uniquely regulated by STAT3 in response to leptin was identified in cells exposed to Entamoeba histolytica., Prostacyclin receptor-dependent inhibition of human erythroleukemia cell differentiation is STAT3-dependent, STAT3 plays a key role not only in cardiac protection but also in the control of cardiac-related inflammation. Review., Targeting both Sp1 and Stat3 is a potential preventive and therapeutic strategy for pancreatic cancer., the possible role of MMP-2/alpha5beta1 interaction in the regulation of alpha5beta1-mediated IL-6/Stat3 signaling activation, The STAT3 silencing by siRNA inhibited the proliferation of AGS human gastric cancer cells through G1 cell cycle arrest, decreased levels of immune-suppressive cytokines, and increased levels of immune-activating cytokines., Data suggest that TSLP might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion., Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo, The role of Phospho- STAT3 as an important independent prognostic marker in node-positive breast cancer patients., the GG genotype might confer increased resistance to standard chemotherapy in acute myeloid leukemia (AML) in the Chinese population, Mechanisms of unphosphorylated STAT3 transcription factor binding to DNA, Both STATs 1 and 3 were highly expressed in cerebral arteriovenous malformation, mainly in the endothelium of AVM blood vessels and perivascular infiltrating inflammatory cells within the nidus., the expression of phosphorylated STAT3 (pSTAT3) in non-small cell lung cancer, PTPMeg2 is an important phosphatase for the dephosphorylation of STAT3., Leukotriene B4 receptor-2 promotes invasiveness and metastasis of ovarian cancer cells through signal transducer and activator of transcription 3 (STAT3)-dependent up-regulation of matrix metalloproteinase 2, EGF-mediated CYR61 upregulation in HES cells involves STAT3 and is counter-regulated by the EGFR/MAPK/ERK pathway., RNAi to diminish expression of ErbB receptors and AP-1 proteins strongly suggested that STAT3 established a balance that maintains the appropriate set of AP-1 proteins and participates in a complex network for regulating keratinocyte differentiation., Activator of transcription 3 (STAT3) pathway is implicated in the production of various cytokines in patients with primary Sjogren's syndrome., Ser727 phosphorylation on STAT3 is not necessarily a secondary event after Tyr705 phosphorylation and suggest that it has a role in the regulation of cell survival activity and nuclear translocation of STAT3 in melanocytic cells., Identify STAT3 as a key molecule for the proliferative response of SMC and neointima formation., Chrysanthemum indicum extract suppressed constitutive STAT3 activation in parallel with the inhibition of constitutive JAK1 and JAK2 activation in human prostate carcinoma cells., Results show that accumulation of pSTAT3-Tyr705 promotes EGFR L858R mutant cell death, thereby confirming the existence of a STAT3-dependent pro-apoptotic pathway in these lung cancer cells., STAT3 might be correlated with tumor differentiation, and its elevated expression may be an adverse prognostic indicator for patients with NSCLC., Pretreatment of tumor cells with STAT3 specific inhibitors or knocking down of STAT3 by SiRNA makes the tumor cell more susceptible to apoptosis and dendritic cell mediated inhibition of both CD24 and HER-2/neu, Expression of pSTAT3 correlates with Her-2 status and CAIX expression and is associated with tumor progression and worse outcome in esophageal cancer, Stage IV melanoma patients without CNS metastasis treated with p-STAT3 inhibitors in efficacy studies should be stratified based on tumor expression of p-STAT3., IL-6 increased IL-21 production by human CD4(+) T cells driving STAT3-dependent plasma cell differentiation., GRIM-19 expression is closely correlated with histological grading and p-STAT3 in hepatocellular carcinoma, PLD acts as an important regulator in Bcl-2 expression by activating STAT3 involving the phosphorylation of Ser727 through the PLA(2)/G(i)/ERK1/2, RhoA/ROCK/p38 MAPK, and Rac1/p38 MAPK pathways., The anticancer effects of celecoxib on nasopharyngeal carcinoma cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway., Abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-alpha production in the presence of suppressive patient plasma., model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein, present study suggests that IL-6 inhibits senescence but promotes the survival and proliferation of tumor cells exposed to DNA damage through the activation of the JAK1-STAT3 signaling pathway, Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells, findings show that Stat3-induced stem cell expansion plays a critical role in the unique clinical progression of invasive bladder cancer through the CIS pathway, The authors have identified IL-6-mediated STAT-3 signalling in CD4 T cells during the earliest clinical phase of rheumatoid arthritis., High phospho-STAT3 expression is associated with mucosal relapse in ulcerative colitis., Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3., Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation., STAT3 signaling pathway may correlate with epigenetic aberrance during gastrocarcinogenesis, Dynamin II function is required for EGF-mediated Stat3 activation but not Erk1/2 phosphorylation, these results demonstrate that in results demonstrate that in human endothelial cells resistin up-regulates SOCS3 expression and activates STAT3 transcription factor., STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway., results suggest that Notch1/STAT3/Twist signaling axis is involved in progression of human gastric cancer and modulation of this cascade has potential for the targeted combination therapy, The SH2 dimerization and activation domain of STAT3 is frequently mutated in patients with large granular lymphocytic leukemia; these findings suggest that aberrant STAT3 signaling underlies the pathogenesis of this disease., present study demonstrates that Ang II induces angiogenic factors production partly via AT1/ JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells, Interleukin 11 regulates endometrial cancer cell adhesion and migration processes via phosphorylation of STAT3, Demonstrate that S1PR1-STAT3 signalling enables myeloid cells to intravasate, prime the distant organ microenvironment and mediate sustained proliferation and survival of their own and other stromal cells at future metastatic sites., beta-catenin pathway regulates miR-21 expression in umbilical vein endothelial cells and glioma cells. This is STAT3 dependent., STAT3 and BLIMP-1 constitute an incoherent feed-forward loop downstream of IL-21 that can coordinate microRNA with mRNA expression during plasma cell differentiation., STAT3 was inactivated in most LMS cases., Interleukin-27 and interleukin-12 augment activation of distinct cord blood natural killer cells responses via STAT3 pathways., STAT1 expression is upregulated by nuclear EGFR and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression., Reduction of miR-21 repressed human telomerase reverse transcriptase expression in a STAT3-dependent fashion, subsequently inhibiting glioblastoma cell growth., STAT3 dimerization at the receptor are essential for the dynamics of early pathway activation., Data show that LIF through STAT3 negatively regulates Th2 differentiation., endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer., The altered JAK2 induced STATs response in human failing cardiomyocytes may be of relevance for the progression of cardiac dysfunction in heart failure., Modulation of STAT-3 in CD4+ T cells affects the differentiation of Th17 cells and Treg cells in patients with rheumatoid arthritis., STAT3 was activated and that the activation could be blocked by an IL-6-neutralizing antibody., Persistent activated STAT3 colocalizes with elevated expression of S1PR1, a G-protein-coupled receptor for sphingosine-1-phosphate (S1P), in the tumor cells of the activated B cell-like subtype of diffuse large B-cell lymphoma., previously unknown STAT3-USP7-P53 molecular network controlling colon cancer development, Targeting Stat3 or Smad7 for knockdown results in resensitization of TGF-beta's cytostatic regulation in vivo., Recurrent bacterial skin and respiratory tract infections were consistently observed in STAT-3 deficient patients., The findings suggest that variants in the STAT3 gene may contribute differentially to susceptibility to rheumatoid arthritis in seropositive and in seronegative patients., STAT3 is aberrantly hypomethylated and overexpressed in hematopoietic stem cells of myelodysplastic syndromes patients., results provide evidence that CD24 regulates STAT3 and FAK activity and suggest an important role of Src in this process., STAT3 protein interacts with Class O Forkhead transcription factors in the cytoplasm and regulates nuclear/cytoplasmic localization of FoxO1 and FoxO3a proteins in CD4(+) T cells., HIV-1 interaction with dendritic cells modulated their functionality, causing them to trigger the activation of the P38MAPK/STAT3 pathway in T cells., H. pylori induced inflammation up-regulate Hath1 expression via interleukin-8/STAT3 phosphorylation while suppressing Hes1, which provides a novel molecular connection between a H. pylori infection and intestinal metaplasia., analysis of the positive link between STAT3 activation and Th17 cell infiltration to the lesional skin in vitiligo vulgaris, Stat3 forms a multiprotein complex with Rac1 and PKC in an hypoxia-reoxygenation-dependent manner., results highlight STAT3beta as a significant transcriptional regulator in its own right, with additional actions to cross-regulate STAT3alpha phosphorylation and nuclear retention after cytokine stimulation, Overview of the role of STAT3 in regulating cellular responses that may contribute to or inhibit pro-fibrotic processes in idiopathic pulmonary fibrosis. [Review Article], IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms., Together these results suggest that the inhibitory effect of OSM on TGF-beta1-induced CTGF mRNA expression is mainly driven by STAT3, thereby providing a signaling mechanism whereby OSM may contribute to tubulointerstitial protection., Targeting STAT3 using a specific inhibitor may be a useful cancer treatment approach, with the potential for a broad clinical impact., Migfilin positively modulates the expression and activity of epidermal growth factor receptor, and Migfilin-mediated migration and invasion depend on epidermal growth factor receptor-induced PLC-gamma and STAT3-signaling pathways., vSOCS inhibits IFN-alpha-induced Stat1/Stat3 signaling., STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia., In the context of thyroid cancer, STAT3 is paradoxically a negative regulator of tumor growth., MLS-2438 inhibits viability and induces apoptosis of human melanoma cells associated with inhibition of STAT3 and Akt signaling., After the cancer cells were incubated with the synthesized PLGA nanocomplexes, PLGA-PEI-TAX-S3SI suppressed Stat3 expression and induced more cellular apoptosis in A549 and A549/T12 cells compared with PLGA-PEI-TAX., Acyloxy nitroso compounds inhibit LIF signaling in endothelial cells and cardiac myocytes, showing that STAT3 signaling is redox-sensitive, STAT3 is involved in sperm functions., the intracellular interaction of IL-32alpha with PKCepsilon and STAT3 promotes STAT3 binding to the IL-6 promoter by enforcing STAT3 phosphorylation, which results in increased production of IL-6., Physiological concentrations of hydrogen peroxide activate hepcidin transcription through signal transducer and activator of transcription 3 protein., The expression levels of STAT3, P-STAT3, and VEGF-C were higher in small cell lung cancer than in normal tissue; STAT3 and VEGF-C play important roles in the development of small cell lung cancers, The results of this study suggested that the STAT3-mediated astrogliosis protects myelin development in neonatal brain injury, STAT3 and STAT5 may function through the IL-6 and IL-2 pathways to play a role in the imbalance of Th17/Treg in NP., Consequently, p27 of hepatitis delta virus activated the signal transducer and activator of transcription-3 (STAT-3) and the nuclear factor kappa B (NF-kappaB) via the oxidative stress pathway., CSE1L- and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL (P<0.001 for all markers). All three markers were associated with patient outcome in DLBCL, apoptosis induced by knockdown of uPAR and MMP-9 is mediated by inactivation of EGFR/STAT3 signaling in medulloblastoma, JAK2 and STAT3 activation is not essential for CCL3, CCL5 or CCL8 induced chemotaxis., GABA may inhibit the growth of cholangiocarcinoma QBC939 cells through the GABAB receptor, and the anti-cancer effects may be partly mediated via the JAK/STAT3 pathway., Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP., Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or DeltaNp63alpha., Uropathogenic Escherichia coli strain-infection decreases STAT3 phosphorylation in 5637 cells., postseptic CD4 T cells are primed toward IL-17 production via increased STAT3-mediated gene transcription, which may contribute to the immunopathology of a secondary viral infection., The results implicated excessive STAT3 signaling in the development of skeletal muscle insulin resistance in type 2 diabetes., a previously unknown link between Wnt3a-mediated activation of STAT3 and cell survival, STAT3 polymorphism can be a predictive marker for treatment with IFN-alpha for patients with metastatic renal cell carcinoma., STAT3 rs1053023 was positively associated with idiopathic recurrent miscarriage in both Bahraini and Tunisian women., STAT3 activation is directly integrated with the receptor tyrosine kinase-GIV-G protein signaling axis., These results provide evidence that activated STAT-1 and STAT-3 regulate VEGF expression indirectly, by modulating HIF-1alpha activity., Results suggested that STAT3-RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death., show that STAT3 directly upregulates the epithelial expression of the inflammatory mediator Toll-like receptor (TLR)2 in gastric tumors, High STAT3 phosphorylation is associated with reduced anti-EGFR-based therapy in patients with metastatic colorectal cancer, Report mechanism of autophagy control that involves STAT3 and PKR as interacting partners., STAT3 is critical for cancer stem cells survival., APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival., these findings revealed a novel functional link between C/EBPbeta and STAT3 that is a critical regulator of endometrial differentiation in women., these results indicate that thrombin might activate c-Src to induce JAK2 activation, which in turn, causes STAT3 activation, and finally induces CCN2 expression in human lung fibroblasts., Using two renal cellular models&SOCS-3 siRNA knockdown,we studied SOCS-3 effects on oncostatin M-induced STAT activation, differentiation and proliferation.SOCS-3 knockdown resulted in enhanced pSTAT1/3 phosphorylation & epithelial diff'n., Data indicate that knockdown of HDAC8 resulted in the increased expression of SOCS1 and SOCS3, and overexpression of SOCS1 and SOCS3 significantly inhibited cell growth and suppressed JAK2/STAT signaling., GRIM-19 inhibits the STAT3 signaling pathway and sensitizes gastric cancer cells to radiation., CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1 macrophage-like cells involve pertussis toxin-insensitive Ga14/16 signaling and IL-6 release., Our results suggest for the first time that the STAT3 gene might be involved in PsA but not in Behcet's disease predisposition., These results suggest a critical association between altered expression of STAT-3 and STAT-5 with SOCS-1 and indicate its potential role as a negative regulator independent of JAK-STAT pathway in tumorigenic transformation of prostate tissue., STAT3 is not crucial for the control of basal cell proliferation and survival of lung carcinoma cells but modulates susceptibility to DNA damaging chemotherapeutics by regulation of intrinsic pro-survival pathways., Leptin/STAT3 signaling is a novel pathway for the up-regulation of hTERT expression in breast cancer cells., HBx activates the Twist promoter by activating STAT3 and promotes epithelium-mesenchymal transition occurrence in liver cells., TCPTP deficiency in human breast cancer cell lines enhances Src family PTKs and STAT3 signaling., The dynamic genome-wide transcriptional responses were nearly identical at early time points following stimulation (when STAT3 is active in response to both IL-6 and IL-10) but divergent at later times (when STAT3 is active only in response to IL-10)., STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter., this is the first study showing the crucial role of NF-kappaB/Stat3 nuclear association in IR-induced ICAM-1 regulation and implies that targeting NF-kappaB/Stat3 interaction may have future therapeutic significance in glioma treatment., ubiquitin ligase TRAF6 negatively regulates the JAK-STAT signaling pathway by binding to STAT3 and mediating its ubiquitination, The functions of TSLP in asthmatic airway remodelling were performed through STAT3 signalling pathway., rs1053023, more so than the STAT3 rs1053004 or JAK2 rs2230724 polymorphisms, is associated with RSM risk., We were able to confirm the presence of STAT3 mutations in large granular lymphocytic leukemia in a high frequency of 72.7%., REVIEW, STAT3 and EIF2AK2 interact and have roles in controlling fatty acid-induced autophagy, interaction between STAT3 and HO-1 abrogates STAT3 activation, and in this way, HO-1 induction represses AR activity, affecting PCa cells tumorigenicity., The present study investigates the involvement of the IL-6 family of cytokines, activation of the transcription factor STAT3 and the role of SOCS3 in regulating excitotoxic neuronal death., Leptin increases HER2 levels by inducing a STAT3-mediated Hsp90 expression in breast cancer cells., examined Stat3 and Stat5 activation patterns in resting and ligand-stimulated primary samples from pediatric patients with acute myeloid leukemia, Xanthohumol is a potent antineoplastic chemo- and radio-sensitizer, and its actions are mediated through STAT3 and EGFR inhibition., High DARPP32/STAT3, DARPP32/STAT5B, and STAT5B/STAT3 ratios were associated with longer patient progression free survival., Data indicate that active cruzipain completely abrogated the STAT3 phosphorylation and enzymatically cleaved gp130 ectodomain., These data demonstrate a nontranscriptional activity of STAT3 that facilitates a crosstalk between proinflammatory cytokine and hemostasis/thrombosis signals in platelets., import of the transcription factor STAT3 into mitochondria depends on GRIM-19, a component of the electron transport chain, Data indicate that tocilizumab enhanced the interferon-induced phosphorylation of STAT1 and inhibited SOCS3 expression and the phosphorylation of both STAT3 and ERK., the unphosphorylated form of STAT3 binds to regulatory regions of proapoptotic genes and prevents their expression in tumor cells but not normal cells, Activation of STAT3 is associated with glioblastoma multiforme., IL-6 trans-signaling-STAT3 pathway may have an integral role in hypertrophic scar pathogenesis., our results suggest that STAT3 exon 21 mutation is rare in most human cancers, reducing EGFR activity strongly reduced pSTAT3 in vivo, Upregulation of Stat3 is associated with gastric adenocarcinogenesis., Malignant pheochromocytoma overexpress HSP90 and STAT3., The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion, ATPgammaS induced COX-2 expression and PGE(2) production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA(2) signaling pathway in A549 cells., RAD001 might have the capacity to induce megakaryocytic differentiation through the up-regulation of STAT3 signalling, Stat3 inhibits WTX expression through up-regulation of micro RNA-370 in Wilms tumor., The depletion of STAT3 inhibited the ability of cells to migrate and invade, and impaired the cellular cytoskeleton mainly microtubules, show that these events can be at least in part attributed to the STAT3/Survivin pathway, Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response., C-reactive protein expression and STAT3 activation are reduced in docosahexaenoic acid and eicosapentaenoic treated HepG2 cells., STAT3 activation was correlated with aggressive behavior of hepatocellular carcinoma and may be mediated via tumor-associated macrophage, Suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of gastrin on human gastric cancer cells., Data indicate that galectin-4 elicits tumor promotion in vitro and in vivo through activation of IL-6/NF-kappaB/STAT3 signaling., SNPs appear to predispose the host with hepatitis B virus mutations to hepatocarcinogenesis., Tumor-derived mutations in the gene associated with retinoid interferon-induced mortality (GRIM-19) disrupt its anti-signal transducer and activator of transcription 3 (STAT3) activity and promote oncogenesis, a novel STAT3 non-consensus TFBS at nt -75/-66 downstream of the NF-kappaB RE in the SAA1 promoter region that is required for NF-kappaB p65 and STAT3 to activate SAA1 transcription, NF-kappaB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells., Blood CD4+CD45RO+CXCR5+ T cells are decreased but partially functional in signal transducer and activator of transcription 3 deficiency., stimulatory effect of ADSC conditioned media or IL-6 was accomplished through activation of both STAT3 and MAP kinse signaling pathways, None of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05)., ECHS1 specifically represses STAT3 activity and negatively regulates the expression of several target genes of STAT3 through inhibiting STAT3 phosphorylation., STAT3 induces PTTG expression to facilitate tumor growth and metastasis., Our data demonstrate that STAT3 is critical in IL-17-induced survival of fibroblast-like synoviocytes from rheumatoid arthritis patients., Data indicate that the mode of binding that is similar to that known for the STAT3 core phosphorylated at Y705., overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion., a new function of DAPK in suppressing TNF-induced STAT3 activation, was identified., Phospho-STAT3 is a marker of favorable outcome in breast cancer patients treated with adjuvant chemotherapy., The tumor suppressive function of arginase-I in both infiltrating and circulating myeloid-derived suppressor cells is a downstream target of activated STAT3., Suppression of STAT3 activity disrupted B-RAF(V600E)-mediated induction of Mcl-1., Interactions between M2 macrophages and endometrial stromal cells via Stat3 activation may play an important role in the development of endometriosis., HBx upregulates the Bax/Bcl-2 ratio by activating the JAK2/STAT3 signaling pathway., antibody behaves like a potent non-competitive inhibitor blocking IL-21 induced STAT3 phosphorylation for a long period of time. These results may help with the translation of preclinical information and dose selection towards ATR-107 clinical efficacy, STAT3-mediated coincidence detection regulates noncanonical immediate early gene induction., Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner., metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. Thus, metformin helps to overcome tumor drug resistance by targeting STAT3., Data indicate that STAT3 physically interacted with progesterone receptor (PR)-A, which is known to be important for uterine development and function, but not with PR-B., Data suggest that inhibition of the JAK/STAT3 signal transduction could be a promising therapeutic target for high-risk pediatric solid tumors., alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation, siRNA-mediated knockdown of DAPK1 attenuated the curcumin-induced inhibition of STAT3 and NF-kappaB. Moreover, DAPK1 suppression diminished curcumin-induced caspase-3 activation., Knocking down BV8 in human myeloid leukemia cells inhibits STAT3 activity and expression of STAT3 downstream angiogenic and pro-proliferation/survival genes., the influence of STAT3 on the IL-17A/IFN-gamma -mediated RNase 7 induction, HCMV activated the IL-6-JAK-STAT3 pathway in PHH and HepG2 cells, STAT3 mutations are frequent in CD30 positive T-cell lymphomas and T-cell large granular lymphocytic leukemia., Androgen-STAT3 activation may contribute to gender disparity in human simply renal cysts., STAT3 directly bound to the STAT3 binding site on the nm23-H1 promoter and activated its expression, Results suggest that the Fas signal favors the Th17-phenotypic features of T cells through the caspase-1/Stat3 signaling pathway., Expression of STAT3 protein in 80 thymic epithelial tumors was detected by immunohistochemistry. Positive expression of STAT3 protein was associated with Masaoka staging and WHO histological classification, but not with age, gender, or tumor size., The IL-6/STAT3 signalling loop and platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor (PDGFR) pathway were important for CM-induced cell migration and invasion., ALK-positive large B-cell lymphomas express a complete plasmablastic differentiation program but unlike plasmablastic lymphomas do not have MYC rearrangements. STAT3 is constantly activated and may be an alternative mechanism to promote MYC expression., STAT3 works with HIF1 to activate HIF1 target genes and to drive HIF1-depedent tumorigenesis under hypoxic conditions, but also has HIF-independent activity in normoxic and hypoxic cells., acetylated STAT3-induced promoter gene methylation accounts for the loss of ARHI expression and cancer cell proliferation., STAT3 phosphorylation was activated more in the GBM-SC lines than serum-derived GB cell lines, reciprocal crosstalk between the MAPK pathway and STAT3-mediated signal transduction forms a critical axis successively activated by lipopolysaccharides in bladder epithelial cells., Stat3 downstream gene product chitinase 3-like 1 is elevated in lung cancer, STAT3 is activated at two phosphorylation sites, Down-regulation of GRIM-19 is associated with STAT3 overexpression in breast carcinomas., Leptin may be one of the proinflammatory cytokines that up-regulates IL-6 production in rheumatoid synovial fibroblasts via activation of JAK2/STAT3., TGF-beta1 up-regulates STAT3 activation and HIF-1alpha stabilization, which leads to TWIST1 expression in a prostate cancer invasion cascade, STAT3 signaling and invasion in human melanoma cell lines is regulated by mitogen-activated protein kinase (MAPK) signaling, High STAT3 expression is associated with acute myeloid leukemia., An interaction between neuroblastoma cells and their microenvironment is mediatwed by the IL-6-STAT3 pathway., miR-124 expression is significantly reduced in glioblastoma and inhibits STAT3., Among signaling pathways that regulate Mcl-1 gene expression, only constitutive STAT3 phosphorylation was suppressed by chrysin., Stat3 is an independent risk factor for subsequent thrombosis during follow-up., Inhibition of the STAT3 pathway by phosphor-valproic acid inhibits pancreatic cancer growth in mice., Data indicate that metastatic breast cancer (BC) cells that failed to activate STAT3 downstream of EGFR did display robust STAT3 activity upon adhesion to fibronectin (FN)., These results suggest that not all patients with Hyper-IgE syndrome who had NIH scores over 40 points carry STAT3 mutations, those whose Th17 cell numbers strikingly decreased probably had autosomal dominant Hyper-IgE syndrome with STAT3 mutations., Taken together, these results suggest that the pharmacological inhibition of STAT3 may be a promising therapeutic strategy for the management of chemoresistance in ovarian cancer., Positive expression rate of IL-6/STAT3 was 39.7% (23/58)/29.3% (17/58) in primary Wilms' tumor tissues, while 61.1% (11/18)/33.3% (6/18) in associated invasive/metastatic tissues., Identification of canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites in the intracellular domain of the interleukin 23 receptor., IL-22/STAT3 signaling pathway may be related to ulcerative colitis and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC., AGK expression was significantly correlated with JAK2/STAT3 hyperactivation in esophageal squamous cell carcinoma, as well as in lung and breast cancer., these results define a novel signaling network whereby JAK2/STAT3 signaling creates a feed-forward loop to raise activated WASF3 levels that promote cancer cell motility., STAT3 binds indirectly in complexes with NF-kappaB to the GADD45G promoter., Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model., STAT3 plays a role in the life cycle of HCV and have clarified the role of STAT3 as a proviral host factor., Elevated levels of IL-26 in human gastric cancer promote proliferation and survival by modulating STAT1/STAT3 signaling., Results suggest that LPLUNC1 can inhibit inflammation and nasopharyngeal carcinoma (NPC) growth by downregulating the Stat3 pathway., STAT3 increases expression of BCL6 and enhances recruitment of RNA polymerase II phosphorylated at a site associated with transcriptional initiation., The presence of activated STAT3 has a profound effect on miR expression in CLL cells., Findings indicate a role of B cells in promoting tumor progression through angiogenesis and identify STAT3 in B cells as potential therapeutic target for anti-angiogenesis therapy., the expression of Oct-4, Nanog, Sox-2 and Stat-3 are related to differentiation in ameloblasts and odontoblasts., Kaposin B significantly contributes to the chronic inflammatory environment by unique activation of the proto-oncogene STAT3, coupled with MK2-mediated inactivation of the STAT3 transcriptional repressor TRIM28., these data indicate a direct role for TEL-AML1, via increasing the activity of RAC1, in regulating the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which results in transcriptional induction of MYC., STAT3 activates miR-155 in chronic lymphocytic leukemia cell, strong STAT3 expression in surgical specimens was correlated with an increase in median colorectal cancer overall survival by about 30 months, Single nucleotide polymorphisms in STAT3 is associated with non-Hodgkin lymphoma., We therefore conclude that germacrone induces apoptosis through the JAK2/STAT3 signalling pathway., Data suggest that flavanoids (naringenin, flavone) suppress STAT3 signaling and induce expression of SOCS3 (suppressor of cytokine signaling 3) in cultured vascular endothelial cells; thus, dietary components can act as anti-inflammatory agents., results suggest that (i) STAT3 is required for the maintenance of the latent state and interference with its functions leads to reactivation and (ii) p300/CBP is essential for HSV reactivation, Our results revealed a novel role of Epstein-Barr virus encoded small non-cdoing RNAs (EBERs) in the coordination of IL-6-STAT3 signaling pathway to chemoresistance and cellular migration in cancer cells., mutation results in impaired host defense against Candida and staphylococci in hyper-IgE syndrome patients, Stat3 inactivation and Skp2 degradation regulate cell death pathways in tumor cell lines treated with salinomycin., Higher expression of p-p38, p-C-JUN, p-STAT3, and p-gp130 in the MBC-B group., High STAT5 expression is associated with pancreatic cancer., The STAT3-induced miR-92a promotes cancer invasion by suppressing RECK., Activation of the EGFR/STAT3 signaling pathway may contribute to lymph node metastasis, which can promote the progression of gastric cancer., Data indicate that SOCS-3, STAT-3, and the status of extragastric nodal metastasis were identified to be the independent factors of the lymph node metastasis from gastric cancer (GC)., The IL-21R/STAT3 pathway is required for many aspects of human CD8(+) T-cell behavior but in some cases can be compensated by other signals., In tumor cells, STAT-3 knockdown inhibited VEGF but not HIF-1alpha expression. HIF-1alpha overexpression increased STAT-3 expression and this was inhibited by ganetespib, The miR-1234 expression level correlated inversely with the expression of STAT3. The Stat3 protein was down-regulated in cells transfected with miR-1234, suggesting that STAT3 might be a potential target for miR-1234., Emodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3., miR-124 was down-regulated specifically in colon tissues from pediatric patients with ulcerative colitis and directly targeted STAT3 messenger RNA, inhibition of IGF-IR and targeting of the JAK2/STAT3 signaling pathway can be a target for ovarian cancer therapy., A novel missense (M206K) STAT3 mutation in diffuse large B cell lymphoma deregulates STAT3 signaling., STAT3 plays a regulatory role in HPV16-mediated cervical carcinogenesis., The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells., These findings uncover a novel mechanism of erlotinib resistance and provide a novel approach to overcome resistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway in human lung cancer, Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3 and STAT3 showed modest associations with BMI in European Americans., The constitutive activation of STAT3 and NF-kappaB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma., IL-18 induces profibrotic cellular changes and collagen production in renal tubular epithelial cells via STAT3 activation., The signaling cross point of the mitochondrial pathway and the JAK2/STAT3 signaling pathway in C6 glioma cell death is modulated by quercetin-nanoliposomes., expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells, STAT3 knockdown reduces cell proliferation., zinc transporter ZIP6 is transcriptionally induced by STAT3 and unprecedented among zinc transporters, and is activated by N-terminal cleavage which triggers ZIP6 plasma membrane location and zinc influx., Data indicate that the anti-tumor effects of guggulsterone (GS) possibly involve multiple networks including inhibition of FAK, Src, and Jak/STAT signaling., The acquisition of B cell stimulating properties by naive cord blood CD4 T cells required the STAT3-dependent expression of ICOS and IL-21., STAT3-mutant Large granular lymphocyte leukemia clones may be responsible for the primary induction of bone marrow failure in a subset of aplastic anemia and myelodysplastic syndromes patients, STAT3 activation promotes oncolytic HSV1 replication in glioma., Data indicate that ruxolitinib effectively inhibited JAK/STAT signalling in hepatocellular carcinoma (HCC) cells with a significant reduction in the expression of JAK downstream targets pSTAT1 and pSTAT3., Data suggest that in prostate cancer cells CDK5 (cyclin-dependent kinase 5) regulates interaction of STAT3 with AR (androgen receptor) through phosphorylation of Ser727-STAT3 and thereby up-regulates AR protein stability., Stat signaling and VEGF expression are inhibited by the antiangiogenic plant flavone acacetin, Data indicate that IL-6- and IFN-alpha-induced STAT3 phosphorylation and IFN-alpha-induced STAT1 phosphorylation were impaired in plasmacytoid dendritic cells (pDCs) from Crohn's disease (CD) patients., Data indicate a mechanism that fibroblast senescence promotes cervical cancer development through high-risk HPV16 and HPV18 E6-activated IL-6/STAT3 signalling in tumour microenvironment., Findings indicate the important role of Stat3 in cisplatin resistance in ovarian cancer., These findings place STAT3 at a critical crossroads between Epstein-Barr virus latency and lytic activation, processes fundamental to Epstein-Barr virus lymphomagenesis., Activated STAT3 binds to the MMP3 promoter region and regulates MMP3 in Heme-induced endothelial cell apoptosis., suppression of STAT3 during brain inflammation would inhibit astrogliogenesis and promote neurogenesis., 92 promotes proliferation and survival of ALK-positive anaplastic large cell lymphoma., Molecular mechanism dissection revealed that targeting prostate cancer cell AR with siRNA promoted cell migration/invasion via CCL2-dependent STAT3 activation and epithelial-mesenchymal transition pathways., Probucol could attenuate tert-butyl hydroperoxide induced mesangial cell senescence by regulating JAK2/STAT pathway., RNA Pol II on HIF1 or HIF2 target genes is primarily associated with HIF1alpha or HIF2alpha in a STAT3 or USF2 dependent manner, results demonstrate the role of IL-6-STAT3 signaling in ACS through increased Th17 cell differentiation, Stat3 activation in lymphoma cells was involved in this cell-cell interaction., Interleukin-6 up-regulates miR-21 levels via activating STAT3 in HBE cells exposed to arsenite., the role of pSTAT3 in temporal bone squamous cell carcinoma warrants further investigation because there is increasing evidence in preclinical models that inhibiting STAT3 phosphorylation can be a useful addition to different anticancer strategies., The total CTGF production induced by TGF-beta in activated HSCs is therefore, to a large extent, dependent on the balance and integration of the canonical Smad3 and Stat3 signaling pathways, Analysis of the STAT3 interactome using in-situ biotinylation and SILAC., STAT3 is an important downstream mediator of the pro-carcinogenic effects of PRKCZ in pancreatic cancer cells., Knockdown of STAT3 causes a significant reduction in tumor burden and delays tumor progression with increased response to gemcitabine., Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine., The STAT3 completely abrogated the anti-apoptotic effect and expression of caspase3 in decidual gammadelta T cells induced by human TSLP., Data indicate that supraglottic laryngeal tumor cell lysates (SLTCL) mediated macrophage polarization is STAT3 dependent., results suggest a two-step mechanism, whereby LfcinB induces TIMP-1 through an IL-11-dependent pathway involving transcription factor AP-1 and STAT3., Gankyrin is crucial for cholangiocarcinoma carcinogenesis and metastasis by activating IL-6/STAT3 signaling pathway through down-regulating Rb protein., targeted by miR-130b, which was further confirmed by the inverse expression of miR-130b and STAT3 in pancreatic cancer samples., RKIP and STAT3 have an additive effect on the survival of high-grade glioma., Expansion of myeloid-derived suppressor cells (MDSCs) by mesenchymal stromal cells (MSC)-secreted HGF involves c-Met (its receptor) and downstream phosphorylation of STAT3, a key factor in MDSC expansion., Data suggest HLA-G antigen regulates invasiveness of choriocarcinoma cells and invasiveness of trophoblasts at blastocyst implantation; down-regulation of HLA-G dampens STAT3 activation; up-regulation of HLA-G promotes STAT3 activation/invasiveness., Studied the cytotoxic effect of NO donors on ovarian cancer cell lines, as well as their effect on posttranslational modification of STAT3 and AKT proteins in these cells., SIRT1-specific short-interfering RNA was used to investigate the role of SIRT1 in STAT3 signaling, our research data indicate that the anticancer function of green tea results from the inhibition of the STAT3 signaling pathway by EGCG., HIC1 interacts with and modulates the transcriptional activity of STAT3., association between STAT3 SNPs and autoimmune thyroid disease was found in chinese patients., Newly synthesized IL-6 drives association of the IL-6 receptor and gp130 with EGFR, leading to EGFR-dependent rephosphorylation of STAT3, which is not inhibited by the continued presence of SOCS3., STAT-3 activation is critical for human plasma cells throughout their maturation., Targeting blockage of STAT3 in hepatocellular carcinoma cells augments NK cell functions via reverse hepatocellular carcinoma-induced immune suppression., Data indicate that the IL-32beta-VEGF-STAT3 pathway affects the migration of MDA-MB-231 cells., Human metapneumovirus infection inhibits the phosphorylation and nuclear translocation of STAT3., Increased IL-6-induced activation of STAT3 was observed in neoplastic gastric tissue, which positively correlated with tumor progression., determined whether activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are dependent on activating mutations of EGFR1 in NSCLC, Ursolic acid inhibits persistently activated STAT3 in cancer stem cells, indicating that STAT3 is a new target for colon cancer prevention., Confluence of cultured lung cancer cells dramatically increases STAT3 activation independent of SRC action., these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis, Cross-talk between KLF4 and STAT3 regulates axon regeneration., We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer., Review of the contribution of STAT3 to lung cancer growth and progression. [Review], EGF, EGFRvIII, STAT3 and STAT5 have roles in progression of glioblastoma, Porphyromonas gingivalis modulates Pseudomonas aeruginosa-induced apoptosis of respiratory epithelial cells through the STAT3 signaling pathway., STAT3 is overexpressed and overactive diffuse large B-cell lymphoma and STAT3 binding associates with oncogenic pathways., results of the activation and varying localisation of STAT3 and its phosphorylated form in nasal polyps suggest that pSTAT3 plays a crucial role in the proliferative development of nasal polyps, KIM-1 expression increased significantly in a manner that corresponded temporally and regionally with increased phosphorylation of checkpoint kinase 1 (Chk1) and STAT3 in acute kidney injury., Data indicate that IL-21 induces IL-2RA (CD25) in normal, but not STAT3-deficient, naive B cells., investigation of STAT3 tyrosine-705 phosphorylation and its correlation with its possible regulator HER2 in the prognosis of pancreatic ductal carcinoma, findings simultaneously reveal how EBV manipulates host STAT3 even before expression of viral oncogenes to facilitate cell survival and proliferation, processes fundamental to EBV lymphomagenesis, An opposing role of AR and STAT3 in prostate Cancer stem-like cell development., This study has confirmed that adrenocortical carcinoma overexpress signal transducer and activator of transcription 3 and insulin-like growth factor 2, mutation is associated with diminishes rates of food allergies and anaphylaxis in patients with autosomal-dominant hyper-IgE syndrome, Thus, our results suggest a previously unknown Stat3-PTPN13 molecular network controlling squamous cell lung carcinoma development, Dominant-negative activity of the STAT3-Y705F mutant depends on the N-terminal domain, that miRNAs represent a newly discovered class of regulatory molecules, investigating their biological functions and contribution to pathologies caused by STAT3 dysregulation is essential to improve our understanding of tumorigenesis, In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling., these findings show that miR-124 functions as tumor suppressor in hepatocellular carcinoma (HCC) by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC., In contrast to naive B cells, STAT3-deficient memory B cells responded to STAT3-activating cytokines, differentiating into plasmablasts and secreting high levels of IgM, IgG, and IgA, as well as Ag-specific IgG., The Multiple myeloma samples seemed to show elevated basal level of Stat3 phosphorylation., TNF-alpha-induced activation of NF-kappaB is sufficient to induce IL-6 expression, activate STAT3, and elevate STAT3 target gene expression in GBM cell lines and human GBM xenografts in vitro., Scoparone might bind the SH2 domain of STAT3., STAT3 activity regulates the cycling of quiescent dental pulp stem cells to determine their fate., Authors have discovered a STAT3-dependent Akt activation that impairs the efficacy of gefitinib., Results demonstrate the remarkable correlation of STAT3 mutation with PRCA, neutropenia and ss2-MG., Restored STAT3 expression through treatment with IL-6 cytokine partly abolished miR-124-mediated cell cycle arrest and apoptosis induction., IL-21 signals through the STAT-3 and STAT- 5b signaling pathway in the CIK cell pool., The autocrine IL-6 pathway induces enzalutamide resistance in prostate cancer cells via the constitutive activation of Stat3., study shows that the MEK-ERK pathway is required for activated Ras-induced phosphorylation of STAT3 on S727, that inhibition of STAT3 S727 phosphorylation contributes to the anti-oncogenic potential of MEK inhibitors, FoxP3 promotes transcription in association with the locus-specific transcription factor STAT3, CD24 mediates gastric carcinogenesis and may promote GC progression by suppressing apoptosis and promoting invasion, with the activation of STAT3 playing a critical role., Targeted blockade of the STAT3 signaling pathway with a decoy oligodeoxynucleotide may represent a potential therapeutic approach in the treatment of ovarian cancer., STAT3 protein expression is a strong indicator of poor prognosis and survival of patients diagnosed with non-small-cell lung cancer. phospho-STAT3(review), Data indicate that CTLA4Fc fusion protein activates STAT3, which is critical for dendritic cells (DCs) function., A panel of miRNAs is regulated through promoter binding of the STAT3 in human macrophage and these miRNAs are involved in anti-apoptosis in response to T. gondii infection., Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human intestinal epithelial cells., The secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties., The SH2 domain of the STAT3 gene is frequently mutated in Asian T-cell large granular lymphocytic leukemia and chronic lymphoproliferative disorders of natural killer cells., These findings uncover a novel mechanism of radioresistance and provide a more effective approach to overcome radioresistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway., The level of p-Stat3 was found to be higher in imatinib therapy resistant cases of chronic myeloid leukemia than in responsive cases, which suggest the beneficial use of p-Stat3 as an indicator to follow the clinical course and the treatment response., These studies demonstrate an important role for STAT3 signaling in ALDH(+) and ALDH(+)/CD44(+)/CD24(-) subpopulations of breast cancer cells., The EGFRvIII-STAT3 pathway promotes cell migration and invasion by upregulating S100A11 in hepatocellular carcinoma., It has been shown that rs3816769 STAT3 gene polymorphisms are associated with Nonsmall cell lung cancer susceptibility and might be regarded as having a significant functional and diagnostic value., activation of STAT3 signaling leads to regulation of hTERT pathway, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705) is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients., This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade., HAVCR/KIM-1 activates the IL-6/STAT-3/HIF-1A axis., (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced ovarian cancer cell apoptosis via NF-kappaB/STAT3 signaling., Syndecan-1 modulates the cancer stem cell phenotype via regulation of the Wnt and IL-6/STAT3 signaling pathways, tumor-specific mutational events in the PTPRT gene can serve as direct drivers for tumor growth by inducing hyperactivation of STAT3, a potent oncogenic transcription factor and PTPRT substrate, in this work, we identified TPCA-1 as a direct dual inhibitor for both IKKs and STAT3, whereas treatment targeting EGFR only could not sufficiently repress NF-kappaB and STAT3 pathways for lung cancers harboring mutant EGFR, vOur study clearly demonstrates that the predominant effect of this combination is the reduction of signaling molecules including STAT3, STAT5b, IGF-1R, VEGF and VEGF-R2 which are involved in the growth, progression and metastasis of human bladder cancer, these data demonstrate that XPO1 inhibition by SINE compounds represses STAT3 transactivation to block the selective oncogenic properties of survivin and supports their clinical use in triple-negative breast cancer ., We demonstrate a mechanism by which EGF promotes prostate cancer cell progression through a ROS/STAT3/HIF-1alpha/TWIST1/N-cadherin signaling cascade, providing novel biomarkers and promising therapeutic targets for prostate cancer cell progression., NF-kappaB and STAT3 signaling pathways, as main inflammatory mediators, are found to be activated in urothelial bladder carcinoma., We propose that the natural compound 2-MS, as a potent dual inhibitor of STAT3 and NF-kappaB pathways, is a promising anticancer drug candidate., our results suggest a previously unknown Stat3-LGR4 molecular network, which may control osteosarcoma development and progression, genetic association studies in Croatian population, Core is capable of up-regulating NANOG expression, Blockage of Stat3 with a selective inhibitor, S3I-201, or siRNA presents an effective strategy to overcome resistance to PI3K/Akt/mTOR inhibition in non small-cell lung cancer cells., data support the existence of a signaling cascade by which stimulation of macrophages with the IL-10 cytokine determines a sequential activation of STAT3 and MafB transcription factors, higher expression of miR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation., Signal transducers and activators of transcription 3 suppression by JMJD2B silencing enhanced DNA damage., Loss of SOCS3 increased tumor growth, migration, and invasion and resulted in accompanied changes in expression of STAT3 and its target oncoproteins., Association of MCL-1 with STAT3 modulates the normal, anti-apoptotic, activity of MCL-1, resulting in pro-apoptotic effects., Inhibition of the STAT3 gene decreases HeLa cell migration, moreover the blocked STAT3 ability to the antyapoptotic gene expression activation leads to the increased susceptibility to apoptotic cell death., study thus identified a mechanism by which STAT3 signaling can be inhibited in pancreatic cancer cells by modifying let-7 expression, This mitoStat3-mtDNA interaction may represent an alternate signaling pathway that could alter mitochondrial function and biogenesis and have a role in tumorigenesis., Data show that T-cell transcription factor GATA-binding protein 3 (GATA-3) expression identifies a subset of T-cell lymphomas PTCL, NOS with a distinct cytokine profile and inferior survival., These findings may provide a novel linkage between the EGFR and STAT3 signaling pathways and the activation of cyclin D1 by LMP1 in the carcinogenesis of NPC., Our data indicate the presence and involvement of Stat3/STAT3-dependent Treg17 cells that specifically target Th17 cells in murine and human crescentic glomerulonephritis., activating mutations specific for large granular lymphocytic leukemia [review], STAT3 and NFkappaB synergistically act for maximum induction of FAT10 expression., downregulation of STAT3 or Survivin can suppress the proliferation of T24 bladder cancer cells., RhoC has a role in regulating cancer stem cells in head and neck squamous cell carcinoma through the over expression of IL-6 and phosphorylation of STAT3, Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein., STAT3 bound to previously undescribed negative regulatory elements within the promoter of PRKCB, which encodes PKCbetaII., NOX1 is involved in acure respiratory distress syndrome pathophysiology and is responsible for the damage occurring in alveolar epithelial cells at least in part via STAT3 signalling pathways., IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma., findings reveal unique structural characteristics of STAT3 within the STAT family and contribute to the understanding of the L78R mutation found in inflammatory hepatocellular adenoma, Inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of esophageal squamous cell carcinoma by facilitating crosstalk between apoptosis and autophagy., In conclusion, here we show that STAT3 activation can be one of the molecular mechanisms leading to KSHV-mediated DC dysfunction, that might allow viral persistence and the onset of KSHV-associated malignancies., Mitochondrial STAT3 plays a major role in IgE-antigen-mediated mast cell exocytosis., The promoter of the miR-17-92 gene cluster is transactivated through the promoter binding of STAT3 while BIM expression is decreasesed during Toxoplasma gondii infection., Cell survival under unstressed conditions is due to cell type-specific autophagy regulation of STAT3 activity., overexpression of hsa-miR-4516 downregulates STAT3, p-STAT3, CDK6, and UBE2N proteins that are consistently upregulated in psoriasis and induces apoptosis in HaCaT cells., A functionally distinct, noncanonical STAT3 phosphoform positively regulates target gene expression in a combinatorial signaling context., Studied a new therapeutic alternative in the treatment of multiresistant lung adenocarcinoma via siRNA-specific transfection of six crucial molecules involved in lung carcinogenesis, Data indicate that proteasomal subunit X PSMB5 is a target of signal transducer and activator of transcription 3 (STAT3)., STAT3 interrupts ATR-to-Chk1 signaling by promoting loss of Claspin, a protein that assists ATR to phosphorylate Chk1., IL-6R/STAT3/miR-34a feedback loop was present in primary colorectal tumors as well as CRC, breast, and prostate cancer cell lines and associated with a mesenchymal phenotype., Phosphorylated STAT3 and PD-1 regulate IL-17 production and IL-23 receptor expression in Mycobacterium tuberculosis infection., STAT3 Tyr705 phosphorylation may have a role in clinical outcome in patients with newly diagnosed supratentorial glioblastoma, data suggest that the pancreatic cancer tumor microenvironment transforms monocytes to monocytic myeloid-derived suppressor cells by STAT3 activation, our results suggest that garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo, NSCLC cells could be sensitized to cisplatin by targeting STAT3 with chemically modified siRNAs together, a fact which was accompanied with increased apoptosis., Data indicate that signal transducer and activator of transcription 3 (STAT3) silenced monocyte-derived dendritic cells promoted a higher interferon gamma production by CD4(+) naive T cells., Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation and migration by upregulating DNMT1 via STAT3 activation., downregulation of LKB1 expression suppresses Stat3 activity that may promote tumor growth during esophageal cancer progression., the present study found that STAT3 (-/p) expression was positively correlated with miR-21 in 60 oral squamous cell carcinoma samples., STAT3 activity is increased in macrophages following mTOR induction, thus contributing to development of atherosclerosis., elevated STAT3 activity in lymph nodes prior to tumor cell arrival may indicate a poorer prognosis in gastric cancer, IL-17 influences the innate immune system in rheumatoid arthritis by increasing the synovial expression of TLR3 via the STAT3 pathway., OSM promotes STAT3-dependent intestinal epithelial cell proliferation and wound healing in vitro., ERK1/2 as well as STAT3 (Ser727) phosphorylation play an important role in LIF-mediated JEG-3 trophoblastic cell invasion and gene expression, Compared to wild-type STAT3, the STAT3 R414K/R417K mutant shows attenuated tyrosine phosphorylation and it is a less active transcription factor., Stat3 activity is regulated by CK2 at its phosphorylation Ser-727 residue., Zn deficiency enhances the acute phase response and particularly the JAK-STAT3 pathway, resulting in increased serum amyloid A production., High STAT3 expression is associated with non-small-cell lung cancer., IFN-alpha, a member of the type I IFN family, differentially modulates TLR7/8- and TLR9-activated STAT3 and ERK in B cells, which provides an explanation for our findings that IFN-alpha enhances TLR7/8-induced, but not TLR9-induced IL-10 production, analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon alpha-globin overexpression, an essential function of Foxm1 in the LIF/Stat3-mediated mESC self-renewal and the generation of iPSCs, work identifies STAT3 binding long noncoding RNA lnc-DC (LOC645683) that regulates dendritic cell (DC)differentiation; lnc-DC bound directly to STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by preventing STAT3 binding to and dephosphorylation by SHP1, Stat3 is a novel substrate of the ring-shaped hetero-oligomeric eukaryotic chaperonin, TRiC/CCT, which contributes to its biosynthesis and activity in vitro and in vivo., our results suggest that the activated Stat3 may represent an important mechanism for Beclin 1 downregulation in nonsmall cell lung cancer development, Endothelial cells from aging individuals have impaired angiogenesis and reduced expression of VEGF likely due to impaired nuclear transport of P-STAT3 and P-CREB transcription factors in these cells., Our study implies that the STAT3 rs2293152 polymorphism may be associated with the occurrence of UC and might be used as a predictive factor for UC in the Chinese Han population., NPM is a downstream effector of the STAT3 signaling, and can facilitate the nuclear entry of phosphorylated STAT3., Zerumbone is a novel blocker of STAT3 signaling., Study provides new insight into the regulation of Epithelial-mesenchymal transition by IL-6 via activation of Stat3 in human cervical carcinoma., High STAT3 expression is associated with neuroblastoma., IL-22 Promotes Colon Cancer Stemness via STAT3 Activation, Mahanine suppresses STAT3 activation and promotes ubiquitin-dependent proteasomal degradation of p-STAT3., HPV-16 E2 may regulate NF-kappaB and STAT3 activation in the presence of TNF-alpha with implications on the survival of HPV-infected cells., the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK which consequently suppresses the activation of STAT3 in non-small-cell lung cancer, activation of STAT3 induces the expression of GM-CSFRalpha that protects CLL cells from apoptosis, suggesting that inhibition of STAT3 or GM-CSFRalpha may benefit patients with chronic lymphocytic leukemia, We reveal that PTPRD is a bona fide tumor suppressor, pinpoint PTPRD loss as a cause of aberrant STAT3 activation in gliomas, and establish PTPRD loss, in the setting of CDKN2A/p16(INK4A) deletion, as a driver of glioma progression., UDP-glucose activates P2Y14 receptor and JAK2, increases STAT3 Tyr705 phosphorylation, and enhances transcription of HAS2., The STAT3 pathway is enhanced during stroke development by IL-32alpha., HPV 16 infection induce upregulation of HER2/neu, pStat3 and IFI16., polymorphisms in STAT3, along with environmental factors, might be associated with the development of gastric cancer., Data indicate that STAT3 transcription factoris a potential target of miR-520a-5p., IL-10 apparently inhibits fibrosis by activating AKT and STAT3 phosphorylation downstream of the IL-10 receptor, Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival, STAT3 rs744166 and rs4796793 polymorphisms may be associated with Crohn's disease occurrence and used as a predictive factor of CD in Chinese Han populations., Inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses the 'stemness' profile in chemotherapy-treated residual ovarian tumor cells in vitro, which is replicated in vivo, leading to a reduced tumor burden., These results support STAT3 signaling activity as another functional marker for human breast cancer stem cells., binding of STAT3 to a predicted STAT3 binding site upstream of the NKG2D gene is enhanced by IL-10 and IL-21, CTLA4 expression is observed in T cells of patients with blood malignancies, and CTLA4(apt)-STAT3 siRNA treatment of immunodeficient mice bearing human T cell lymphomas promoted tumor cell apoptosis and tumor growth inhibition., Atopic dermatitis patients showed significantly higher nTreg-cell counts compared to STAT3-hyper-IgE syndromes and control individuals, For all the three STAT3 constructs., LKB1 is differentially regulated by PRL at the level of transcription in representative human breast cancer cells. Its promoter is targeted by STAT3 and STAT5A, and the cellular estrogen receptor status may affect PRL-responsiveness, Molecular docking analysis suggested that compound 1 might putatively function as an inhibitor of STAT3 dimerization by binding to the SH2 domain., RECK controls this angiogenic rheostat through a novel complex with cell surface receptors to regulate STAT3 activation, Data demonstrate that the serum levels of SOCS3 and STAT3 were increased in childhood atopic dermatitis (AD) compared with controls., miR-221 and miR-222 act in a positive feedback loop to increase expression levels of RelA and STAT3 in colorectal neoplasms. Antagonism of miR-221 and miR-222 reduces growth of colon tumors in mice with colitis., Among all women, there was a positive correlation between JAK2 and STAT3 expression, Data indicate that fucoidan induces apoptosis through the down-regulation of signal transducer and activator of transcription 3 (p-Stat3)., data presented herein confirmed the occurrence of a redox-dependent regulation of STAT3, identified the more redox-sensitive cysteines within STAT3 structure, and may have important implications for development of new drugs, FGF2 is required for motor neuron differentiation from human neural stem cells and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis., The IL-6-STAT3 axis mediates a reciprocal crosstalk between cancer-derived mesenchymal stem cells and neutrophils to synergistically prompt gastric cancer progression., AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers, 6SG also suppressed the expression of STAT3-regulated gene products., STAT3 pathway plays an important role in mediating tumor-initiating capacities in nasopharyngeal carcinoma and suggest that inactivation of STAT3 with EGCG may represent a potential preventive and therapeutic approach., Data indicate that ubiquitin specific peptidase 22 (USP22)-mediated sirtuin 1 (SIRT1) deubiquitination inhibits STAT3 transcription factor acetylation and its transcriptional activation., Activation of STAT3 protein leads to uncontrolled cell proliferation., STAT3 provides a negative-feedback safety mechanism that limits tissue damage by T helper (Th)17 cells during chronic inflammation, demonstrating that active STAT3 in high density cultures may enhance the formation of IL-17-producing memory T cells., Suppression STAT3 signaling is implicated in kurarinol-mediated hepatocellular cell apoptosis., HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells., Common variations of STAT3 could significantly affect the risk of obesity and hypertriglyceridemia in Chinese Han population., the high proportion of pSer727-STAT3 positive neoplastic cells in glioblastoma is an independent unfavorable prognostic factor, Our data indicate that expression of both CD44s and pSTAT3 in clear cell renal cell carcinoma is associated with advanced tumor stage and patient survival, data thus provide important and novel insights into the roles of MRTF-A and STAT3 in regulating MDA-MB-231 cell migration., The critical role of STAT3 in autoimmune disease., Pretreatment with a STAT3 inhibitor also augmented SRP induced growth inhibition and cell apoptosis., Investigated the effects of mTOR-STAT3 pathway on the invasion and migration of hepatoma cells., IL-22 conferred resistance to 5-FU and OXA by inducing IL-8 autocrine expression through STAT3 activation., RelB-p52 dimers were found to directly bind to the IDO promoter, leading to IDO expression in MDSCs, Many drug-treated oncogene-addicted cancer cells engage a positive feedback loop leading to Stat3 activation., MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the Epithelial-mesenchymal transition of breast cancer stem cells by down regulating the STAT3 pathway, ISL-1 is tightly linked to non-Hodgkin lymphoma proliferation and development by promoting c-Myc transcription, and its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex activation., Suggest tectochrysin leads to apoptotic cell death in NSCLC cells through activation of DR3 and Fas expression via inhibition of STAT3 phosphorylation., Data support a model in which EWS/FLI1 deficiency results in the secretion of soluble factors, such as IL6, which activate STAT3 in bystander cells that maintain EWS/FLI1 expression., in human HCC tissues, SPTBN1 expression correlated negatively with expression levels of STAT3, ATF3, and CREB2; SMAD3 expression correlated negatively with STAT3 expression, TLR9 ligands induce S100A8 in macrophages via a STAT3-dependent pathway which requires IL-10 and PGE2., STAT3 is negatively regulated by lupeol, inhibiting growth and inducing apoptosis, in hepatocellular carcinoma cells., STAT3 signaling in human cancer cells is blocked by N6-substituted adenosine analogues, a novel class of JAK2 inhibitors, STAT3 and MMP-2 have a role in the diagnosis of colon adenocarcinoma and the detection of the degree of differentiation, Low PIAS3 expression in malignant mesothelioma is associated with increased STAT3 activation and poor patient survival., This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for Colorectal cancer therapy., ATF4 may promote multidrug resistance in esophageal squamous cell carcinoma cells through the up-regulation of STAT3 expression, These data suggest that the STAT3 locus is associated with both inflammatory bowel disease and colon cancer, STAT3 is a critical signaling node in BCR-ABL1 tyrosine kinase-independent leukemia resistance that is reversed by a discovered BP-5-087., Gain-of-function and loss-of-function studies with cultured mouse and human basal cells suggest that IL-6/Stat3 signaling promotes ciliogenesis at multiple levels., STAT3 binds to the -201 to -210 region of PRL-3. STAT3 functionally regulates PRL-3. STAT3 core signature was enriched in AML with high PRL-3 expression. The STAT3/PRL-3 regulatory loop contributes to the pathogenesis of AML., These findings demonstrate a distinct role for STAT3 signaling in basal breast cancers, and underscore the importance of considering subtype-specific molecular pathways that contribute to tissue-specific cancers., AngII/Rac1/STAT3 signaling as a mechanism for atrial structural remodeling, the inhibition of STAT3 signaling by NDRG2 suppresses EMT progression of EMT via the down-regulation of Snail expression, Factors released by CBMSCs protect endothelial cells from the deleterious impact of GSD by activation of the STAT3 survival pathway, These results illustrate the novel activity of the C5a-C5aR axis that promotes human NPC cell proliferation through PCAFmediated STAT3 acetylation., IL-10/Janus kinase/STAT3 signaling dysregulates Bim expression in autoimmune lymphoproliferative syndrome., Expression of p-STAT3 is upregulated in peripheral CD4+ and CD8+ T cells of hepatocellular carcinoma patients., Incubation of hepatocarcinoma cell lines with tocilizumab or knockdown of signal transducer and activator of transcription 3 reduced the ability of macrophages to promote sphere formation by CD44+ cells., Both Stat3 and Stat5 mediate trans-activation and epigenetic remodeling of IL10 through their interaction with the histone acetyltransferase p300., TRPM7 activates JAK2/STAT3 and/or Notch signaling pathways and leads to increased cell proliferation and migration., The present study concluded that IL-27 reduces lipid accumulation of foam cell by upregulating ABCA1 expression via JAK2/STAT3., results suggest that GPR30 is the estrogen receptor that mediates the anorectic effect of estrogen through the STAT3 pathway in the hypothalamus, NTS/IL-8/CXCR1/STAT3 signaling is crucial for the maintenance of stem-like traits in glioblastoma stem cells ., Data suggest that STAT5A and STAT5B (highly conserved genes; 96% identity in amino acid sequences) are nearly identical in responses to growth hormone; STAT1 and STAT3 exhibit weaker binding to DNA elements in insulin-like growth factor-I gene., IL-22 activates miR-197 expression through the binding of phosphorylated STAT3 to sequences in the putative promoter of miR-197., By inducing autophagy via the ERK/AKT-mTOR-STAT3-Notch signaling cascade., In addition to IL-6, TNF-alpha increases Stat3 and NFkappaB binding to the fascin promoter to induce its expression., Unphosphorylated-STAT3 plays an important role in angiotensin II-induced gene expression and in the consequent development of cardiac hypertrophy and dysfunction., The present study provides compelling experimental evidence that Ang-II/AT1 receptor/STAT3 is an important signaling pathway in the atrial myocardium., The data revealed a protective role of autophagy in the radiosensitizing effects of STAT3 inhibition, and inhibition of both autophagy and STAT3 might be a potential therapeutic strategy to increase the radiosensitivity of glioma cells., ER stress induced endogenous expression of CCL5 via elevating U-STAT3 expression; however, ER stress inhibited CCL5 secretion, which in turn, decreased the transmigration of breast cancer MCF-7 cells., IL-6 has a major role in activating breast stromal fibroblasts through STAT3-dependent AUF1 induction, Results suggest that piperine may exert at least part of its anti-cancer effect by controlling interleukin-6 (IL-6) expression through the suppression of p38 MAPK and STAT3 protein., A novel IL-6/Stat3-miR-17-92 cluster-PTEN signaling axis is crucial for cholangiocarcinogenesis and tumor progression., To be associated with signal transducer and activator of transcription 3 pathway inhibition., High Stat3 protein expression is associated with lung cancer., STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma., Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering., Data suggests that targeting both tumor initiating and differentiated cell populations by STAT3 inhibition is predicted to have greater efficacy for prostate cancer treatment., NDRG2/gp130/STAT3 pathway can mediate the antimetastatic effects of Dp44mT in hepatocellular carcinoma., ZER suppressed EGF-induced CD44 expression through inhibition of the STAT3 pathway. Therefore, we suggested that ZER may act as a promising therapeutic drug for the treatment of breast cancer., STAT3 activation in T-cells with neoplastic morphology is associated with the presence of eosinophils in situ and that malignant T-cell lines produce activators of eosinophils through both STAT3-dependent and -independent pathways., IL-32theta;, through its interaction with PKCdelta, downregulates CCL5 expression by mediating the phosphorylation of STAT3 on Ser727 to render it transcriptionally inactive., STAT3 mutations are associated with large granular lymphocytic leukemia progression., results demonstrated that feedback activation of the IL6-STAT3 loop lead to acquired resistance to PI3K inhibitors by promoting EMT and CSC-like features, associations between STAT3 rs744166 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease, Mitochondrial pSTAT3Ser(727) is part of the antioxidant defense pathway of chronic lymphoid leukemia B cells that regulates their viability., Targeting the CXCL12-CXCR4/JAK2/STAT3 signaling pathway may be a potential therapeutic strategy for the treatment of breast cancer., RRAD promotes EGFR-mediated STAT3 activation and induces temozolomide resistance of malignant glioblastoma., CCL2 greatly enhanced IL-6-induced EMT events mainly by upregulating the expression of Twist. Genetic or pharmacological inhibition of STAT3 disrupted STAT3-centered loop and markedly suppressed Twist expression as well as IL-6/CCL2-mediated EMT induction, On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein 3 (Sp3) transcription factor exchange and recruitment of p300., LIF has a role in negatively regulating tumour-suppressor p53 through Stat3/ID1/MDM2 in colorectal cancers, Suggest that feedback activation of STAT3 via up-regulation of MUC1/4 expression constitutes a key node mediating trastuzumab resistance., CYP2E1 expression regulation occurred via a transcriptional mechanism involving STAT3., Data suggest that RKIP inhibits gastric cancer metastasis via the downregulation of its downstream target genes STAT3 and cyclin D1., pSTAT3-VEGF signaling pathway, which is correlated with peritumoral edema extent, might be a regulatory mechanism in the course of peritumoral edema formation during glioblastoma tumorigenesis and progression., In addition to its established role as a transcription factor in cancer, STAT3 regulates mitochondrion functions, as well as gene expression through epigenetic mechanisms. [review], Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs., The STAT3/beta-catenin interaction is complex but may reduce the proliferative activity of beta-catenin possibly by taking beta-catenin protein beyond the optimal level., results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, These results suggest that calpain plays an important role in E. histolytica-induced degradation of NF-kappaB and STATs in colonic epithelial cells, which ultimately accelerates cell death., STAT3 activation is related to the up-regulation of miR-17-92 clusters in retinoblastoma cells via positive feedback loop between them, These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder., Activation of miR-21 by STAT3 induces proliferation and suppresses apoptosis in nasopharyngeal carcinoma by targeting PTEN gene, JAk2/STAT3 plays a key role in CCR7 regulatingSquamous cell carcinoma of the head and neck metastasis., our results show that 20(S)Rg3 inhibits the Warburg effect by targeting STAT3/HK2 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)Rg3 to be used as a therapeutic agent for ovarian cancer, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway., Stat3, phosphorylated Stat3, and MMP2 were overexpressed in esophageal squamous cell carcinoma (ESCC) and associated with invasion of ESCC. Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter., High STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer., BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells., Studied the possible relationship between STATIP1, STAT3 and CML resistance., Data show that cultured keratinocytes treated with STAT3 transcription factor inhibitor (Stattic) survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release., CD147 has a role in promoting Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells, Cten expression mediates invasion of human lung cancer cells and is upregulated by epidermal growth factor via STAT3., High STAT3 expression was associated with pancreatic cancer., High serum leptin may reduce endometrial receptivity by activating the STAT3 signal pathway and down-regulating gamma-ENaC expression in the endometrium., SOCS3 and STAT3 are the major controllers of the outcome of infection with Mycobacterium tuberculosis. (Review), reveal a novel role for E2 in regulating the activities of NF-kappaB and STAT3 that may have implications in carcinogenic progression of HPV16-infected cells under conditions of stromal inflammation, High SMYD3 and pSTAT3 expressions may indicate poor prognosis of patients with gastric cancer, These findings suggest that INPP5F is a potential tumor suppressor in gliomas via inhibition of STAT3 pathway, and that deregulation of INPP5F may lead to contribution to gliomagenesis., The results provide evidence that the regulation of IL-6, IL-10, c-Jun, and STAT3 gene expression in Chronic lymphocytic leukemia B cells is clearly different from normal B lymphocytes., Mechanical stretch upregulated fibronectin and TGF-beta1 expression and activated STAT3 in proximal renal tubular epithelial cells., Our findings demonstrate that leptin-induced STAT3 is partially cross activated through SK1-mediated IL6 secretion and gp130 activation. Positive correlations in human tissues suggest the potential significance of this pathway in ER-negative breast cancer, Endocytic AMR controls TPO expression through Janus kinase 2 (JAK2) and the acute phase response signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, These results indicated that STAT3 and STAT5b polymorphisms might be a candidate pharmacogenomic factor to assess susceptibility and prognosis in breast cancer patients., Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorgammaT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung, signalings can reciprocally and positively regulate each other, leading to enhanced non-small cell lung cancer (NSCLC) cell proliferation and survival., this study identified a marked activation of Human beta-defensin-2 expression in human alveolar epithelial type II cells by IL-22 through STAT3-dependent mechanisms., STAT3/miR-21 axis could be a candidate therapeutic target for OSCC chemoresistance., Data indicate that ethanol extract from Sedum sarmentosum (ESB) inhibits HepG2 cell proliferation and induces apoptosis by inhibiting signal transducer and activator of transcription 3 (STAT-3) signaling., our findings suggest that miR-124 functions as a tumor suppressor by targeting STAT3, and that miR-124 may potentially serve as a useful biomarker for the prognosis of non-small cell lung cancer patients., Cigarette smoke-induced MMP2 and MMP9 secretion from aortic vascular smooth cells is mediated via the Jak2 and Stat3 pathway, Results demonstrate existence of a functional loop involving Let-7a, STAT3 and miR-21 which were found potentially regulated by viral oncoprotein E6., A novel mutation in the STAT3 in Hyper IgE syndrome is reported, Notch1 promotes epithelial-mesenchymal transition and the cancer stem cell phenotype through induction of STAT3., Curcumin and epigallocatechin gallate specifically inhibit STAT3 phosphorylation in cancer stem cells., STAT3 and cyclinD1 correlate with more aggressive tumor behavior in esophageal squamous cell carcinoma. When STAT3 and cyclinD1 are considered together, they serve as effective prognostic markers in patients with surgically resected ESCC., Stat3 was found to directly interact with 14-3-3zeta and its disruption relieved the inhibition induced by 14-3-3zeta in tumor inflammation; study provides evidence that 14-3-3zeta may regulate tumor inflammation and immune response through Stat3 signaling in oral squamous cell carcinoma., Suggest that under conditions of sustained increases in hexosamine biosynthetic pathway activity there is an increase in basal STAT3(Y705) phosphorylation that cannot be further increased by leptin., the present study revealed the aberrant expression of STAT3 and miR21 in hepatocellular carcinoma side population cells., Our data suggested that tumor-associated macrophages might induce drug resistance through IL-10/STAT3/bcl-2 signaling pathway, increased activity in the IL-15-derived dendritic cells has a key role in their high effector function, STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells, MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-beta/Smad2/STAT3/STAT5 pathway, Butein ameliorated colitis in IL-10(-/-) mice by regulating IL-6/STAT3 and MMP-9 activation., MicroRNA-19a functions as an oncogenic microRNA in non-small cell lung cancer by targeting the suppressor of cytokine signaling 1 and mediating STAT3 activation, Suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer., Phosphorylated placental STAT3 is increased in women with polycystic ovary syndrome., STAT3 inhibitor OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC., STAT3 signaling has a role in quercetin-induced endoplasmic reticulum stress that enhances cDDP cytotoxicity in ovarian cancer, PTPRK underexpression leads to STAT3 activation and contributes to nasal NK/T-cell lymphoma pathogenesis, STAT3 overexpression reduced E-cadherin and beta-cadherin. It enhanced N-cadherin and vimentin expression in SMMC7721 cells. STAT3 may bind the Twist promoter, mediate its transcriptional activity, and then promote the EMT in SMMC7721 cells., Taken together, these results illustrate that, as a potent inhibitor of HIF-1alpha and Stat3 signaling, LB-1 exhibits antitumor effect and could be potentially used to treat pancreatic cancer., pSTAT3 Y705 is increased in T4 cells among human recipients of allogeneic HCT before the onset of Grade II-IV acute GVHD. STAT3 signaling and resultant Th17 tissue accumulation are associated with acute GVHD onset, severity, and treatment outcome., High STAT3 expression is associated with the pathogenesis of myeloproliferative neoplasm., fad104 suppressed the invasion and metastasis of melanoma cells by inhibiting activation of the STAT3 signaling pathway, Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, PDLIM2 repression is essential for KSHV-induced persistent activation of nuclear factor kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) and subsequent tumorigenesis and tumor maintenance, To drive STAT3 activation and EMT through STAT3-mediated TWIST1 induction., The overexpression of B7-H3 induces resistance to apoptosis in colorectal cancer cell lines by upregulating the Jak2-STAT3 signaling pathway, SOCS3 negatively regulates proliferation and angiogenesis of NCI-H446 cells and that HIF-1alpha is required in this process. The results also suggested a suppressive role of SOCS3 in Akt signaling, but not STAT3 signaling to block HIF-1alpha expression, the expression of IL-6 was significantly higher in MBT-SCs. Additionally, the expression of STAT3 in MCF-7 cells increased slightly when they were co-cultured with malign breast tissue-derived stromal cells, revealed a tri-lateral relationship among HPV infection, Stat3 activity and IL17 level, whose collaborative act may orchestrate a proinflammatory microenvironment in the colorectum that may promote carcinogenesis and possibly facilitate progression of CRC, Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction., STAT3 functions via cellular PCBP2 to regulate B-cell lytic susceptibility by restraining Epstein-Barr Virus lytic activation., Targeted bovine-derived proteins were evaluated for their effects on signal transducer and activator of transcription-3 (STAT3) phosphorylation in human skeletal muscle cells., STAT3 controls NF-kappaB-induced IL-8 expression by sequestering NF-kappaB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression., Authors identified nuclear pSTAT3 expression in 59.76 % of tumors. pSTAT3 expression was correlated with differentiation degree of tumors, lymph node metastasis status, clinical stage of tumors and the prognosis of NSCLC patients after resection., Noncanonical STAT3 activation regulates excess TGF-beta1 and collagen I expression in muscle of stricturing Crohn's disease., GP130/STAT3 pathway is activated in NAFLD and can worsen insulin resistance while protecting against other lipotoxic mechanisms of disease pathogenesis., We conclude that OSM-mediated signaling contributes to aggressive nature associated with mesenchymal features via STAT3 signaling in glioma cells., aberrant activation of STAT3 signaling plays an important role in the pathogenesis of endometriosis, this study proposes the existence of an aberrant IL-6/STAT3/Fra-1 signaling axis leading to colorectal cancer aggressiveness through epithelial-mesenchymal transition induction, Decreased Stat3 expression and activation may play an important role in the pathogenesis of preeclampsia., This study collectively showed that Polygonum flavonoids could induce liver carcinoma cell apoptosis both in vitro and in vivo., Efficacy of the FLLL32 pharmacological inhibitor in delaying OS growth suggests that targeting JAK2/STAT3 may be a potential therapeutic strategy for patients with OS., STAT3-driven transcription is dependent on dimethylation of K49 by EZH2, functions as a co-activator for nuclear activity of RelB/p52 in positive regulation of pro-labor genes in the placenta, Increased expression of STAT3 was associated with metastases in Colon Carcinoma., Pituitary adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression., Its signaling pathway plays a role in tumor angiogenesis., Genetic variants of STAT3 might contribute to anti-tuberculosis drug-induced hepatitis susceptibility in Chinese Han population., In this study, nifuroxazide not only decreased expression of Stat3 phosphorylation at tyrsione residue 705 but also downregulated MMP-2 and MMP-9 expression in 4T1 cells., Report diffuse expression of STAT3 in gastric adenocarcinomas., macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-kappaB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice., Data show that calcitriol inhibited interleukin 6 (IL6) in association with an attenuation of STAT3 transcription factor activation., Constitutive activation of STAT3 is associated with myeloproliferative neoplasm., The role of STAT3 in tumorigenesis, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells., Aberrant STAT3 and HIF1a activity drives tumor progression in malignant peripheral nerve sheath tumors., PAR3-mutant proteins exhibit a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions and activate STAT3 at cell confluence., Jak1/Stat3 activation may mediate the activation of NF-kappaB and the expression of IL-8 in H. pylori-infected AGS cells., there is a regulatory pathway consisting of miR-30, SOCS3, and Jak/STAT3 in GSCs, and targeting this pathway may be a promising strategy to treat glioma., we defined a role for activated STAT3 and G9a histone methyltransferase in epigenetic silencing of miR-200c, which promotes the formation of breast CSCs defined by elevated cell surface levels of the leptin receptor, Simultaneous silencing of beta-catenin and STAT3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells., active forms of STAT3 (pSTAT3) and GSK-3beta (pGSK-3beta) were found in 68 (25%) and 124 (46%) of 267 gastric cancer cases, respectively, showing a positive correlation (p < 0.001), SIRT1 and STAT3 expression protects retinal pigmented epithelium cells against oxidative stress., These findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status., Delta tocotrienol treatment inhibits ETK phosphorylation level and induces SHP-1 expression, which correlates with downregulation of STAT3 activation., Myricitrin treatment protects endothelial cells from ox-LDL-induced endothelial cell apoptosis, which results in reduced atherosclerotic plaque formation, via STAT3 signaling., MRTF-A and STAT3 synergistically recruited DNMT1 to hypermethylate the promoter of BRMS1 and affect the expression of BRMS1.MRTF-A and STAT3 promote breast cancer cell migration via hypermethylating BRSM1., Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer., Study demonstrates that HPV+ and HPV-head and neck squamous cell carcinoma(HNSCC) are differentiated by the activity of key transcription factors (TFs) including STAT3 and NF-kappaB. Approximately 25% of primary HNSCC, almost exclusively HPV-, have these TFs and their targets coordinately upregulated., Findings suggest a crucial roles for resistin, IL-6 and STAT3 in breast cancer racial disparity., Capsaicin-induced apoptosis in pancreatic cancer cells was associated with inhibition of beta-catenin signaling due to the dissociation of beta-catenin/TCF-1 complex and the process was orchestrated by STAT-3., CD4 T cells from patients with RA have abnormal functional networks in STAT3 signaling and Wnt signaling., Data suggest that STAT Transcription Factors STAT1 and STAT3 defects have different effects on trained immunity., Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells., Endogenous PML suppresses interleukin (IL)-6-induced gene expression as well as phosphorylation and transcriptional activation of STAT3 in hepatoma cells., Identification of a novel tumor-promoting function for IGFBP2 of activating EGFR/STAT3 signaling and facilitating EGFR accumulation in the nucleus, thereby deregulating EGFR signaling by two distinct mechanisms., STAT3 and STAT5A were bound to the xCT promoter., Our results suggest the significance of STAT3 activation in the maintenance and survival of ovarian cancer cells, findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway., ferristatin II synergized with BMP6 and IL-6 to enhance hepcidin expression in vitro, However, this synergy was not due to activation of either Smad or Stat3 signaling, Polymorphism in STAT3 gene is not associated with cervical cancer., miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway., weak RELA-activation signals (CD40L, LPS) depended on IFN-gamma induced STAT1/IRF1/IRF8 co-signalling, which was completely blocked by JAK inhibitors as reported before, STAT3 signaling downstream of IL-23R and IL-21R has a role in controlling human mucosal-associated invariant T cells and NKT cell numbers, we demonstrated that recombinant human OSM (rhOSM) promoted tumor angiogenesis in EC cell lines by activating STAT3 (signal transducer and activator of transcription 3) and enhanced both cell migration and cell inva, STAT3 acts as a mediator that synergizes TGF-beta and Ras signals, mutations result in hyper-IgE syndrome, which is treated by hematopoietic stem cell transplantation, Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway., we demonstrate the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3siRNA delivery strategy to alleviate MDSC-mediated immunosuppression, These results show that temporarily increasing STAT3 activity is sufficient to reprogram human pluripotent stem cells to naive-like pluripotent cells., these findings indicate that constitutive IL6/STAT3 pathway activation is important in driving tumor growth and inflammatory cross-talk with myeloid cells within the Group A EPN microenvironment., Our study found that STAT3 rs4796793 polymorphism plays an important role in influence the development and overall survival of breast cancer patients., STAT3 mediates GRP78-promoted breast cancer cell growth and migration., STAT3 inactivation reverses the glycolytic shift by down-regulating key enzymes and that it induces up-regulation of latexin as a tumor-suppressor molecule, which partially results in cancer cell apoptosis and tumor growth suppression., PTPRT promoter methylation is significantly associated with sensitivity to STAT3 inhibition in HNSCC cells, suggesting that PTPRT promoter methylation may serve as a predictive biomarker for responsiveness to STAT3 inhibitors in clinical development, With the exception of one line of activated B cell Diffuse Large B Cell Lymphoma cells, the four variants were found in roughly the same ratios despite differences in total levels of STAT3 transcripts., The activation of Fas signaling promoted cell migration and resulted in STAT3-dependent Fascin upregulation in AGS gastric cancer cells., Protein and mRNA levels of PCBP2 were down-regulated under insulin-resistant conditions. Over-expression of PCBP2 inhibits HIF1alpha and STAT3 pathway., Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers., results suggest that SIPAR terminates the activation of STAT3 through a dephosphorylation process that is dependent upon interaction with TC45 in the nucleus, sorafenib and SC-1 ameliorate liver fibrosis through STAT3 inhibition in HSC and STAT3 may potentially serve as a promising fibrotic biomarker and target in liver fibrosis, activation of Src/STAT3/HO-1/autophagy signaling pathway might play a general role in protecting certain subtypes of breast cancer cells from doxorubicin-induced cytotoxicity, Histone acetyltransferase inhibitor C646 reverses epithelial to mesenchymal transition of human peritoneal mesothelial cells via blocking TGF-beta1/Smad3 signaling pathway in vitro., miR-21 and let-7a function as clinically relevant integral components of STAT3 signaling., Lethe, which was upregulated by activated STAT3, may promoting the replication of HCV through a negative regulatory mechanism of type I IFN response., STAT3 phosphorylation is increased following overexpression of miR-155 in CD4+ T cells., meta-analysis suggests that the STAT3 rs12949918 and rs744166 polymorphisms, but not other three polymorphisms, may be an important protective factor for cancer, Results suggest that STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in primary central nervous system diffuse large B-cell lymphoma, Increased ADMA may lead to manifestation of pulmonary hypertension phenotype in human endothelial and smooth muscle cells via the STAT3/HIF-1alpha cascade., STAT3 protein regulates vascular smooth muscle cell phenotypic switch by interaction with myocardin and SRF., In arsenite-transformed HaCaT (HaCaT-30T) cells, down-regulation of STAT3 by siRNA blocked the process of epithelial-mesenchymal transition and decreased their neoplastic properties that were antagonized by over-expression of miR-21., Paeoniflorin inhibits cell viability and induces apoptosis through the up-regulation of miR-124 and suppression of PI3K/Akt and STAT3 signaling in gastric carcinoma cells., STAT3 signaling is a key element that regulates keratinocyte differentiation., The gp120-triggered modulation of miR expression via STAT3 activation., our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in cancer stem cell markers, RPTS can significantly promote apoptosis in SW480 colorectal cancer cells. The mechanism may be that it suppresses the secretion of IL-6 and inhibits the IL-6/JAK-STAT3 protein signaling pathway., Expression analysis revealed upregulation of IL6 and CD126 and GP130 in ALDH(hi) endometrial cancer ... targeted inhibition of the IL6 receptor and its downstream effectors JAK1 and STAT3 reduced tumor cell growth., gene deficiency is associated with vasculopathy, Data show that both signal transducer and activation of transcription factors STAT5 and STAT3 were activated in significant percentages of cells in atypical ductal hyperplasia (ADH)., cardamonin is a novel inhibitor of STAT3 and has the potential to be developed as a new anticancer agent targeting Glioblastoma stem cells ... targeting STAT3 signal pathway is an important strategy for the treatment of human glioblastoma multiforme, B7H3 promotes cell migration and invasion through the Jak2/Stat3/MMP9 signaling pathway in colorectal cancer, JAK2/STAT3 inhibitor AG490 inhibited the leptin-induced migration, invasion and MMP-2 expression in endometriotic cells. Leptin does this via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway., Our results suggested that STAT3 phosphorylation is involved in PLCe-mediated inflammatory cytokine release, STAT3 activation may induce invasion and metastasis through the mediation of epithelial-to-mesenchymal transition in hepatocellular carcinoma cells., Single Nucleotide Polymorphism rs1053004 in STAT3 gene is associated with Susceptibility to Hepatocellular Carcinoma with Chronic Hepatitis B., These results suggest that STAT3 inhibition, by down-regulating the expression of HSF1/HSP70, reduces Mcl-1 and leads to both apoptosis and autophagy induction in PEL cells., Study demonstrate that STAT3 rs744166 G allele is associated with increased risk of gastric cancer in a Western population., Mutations leading to constitutive active gp130/JAK1/STAT3 pathway., miR-204 targets JAK2 and suppressed JAK2 and p-JAK2 expression in breast cancer, which further inhibit the activation of STAT3, BCl-2 and survivin., Glycyrrhizic acid inhibits leukemia cell growth/migration by blocking AKT/mTOR/STAT3 signaling., STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases., Both studied polymorphisms in the STAT3 gene seem to play a significant role in susceptibility to Hashimoto's thyroiditis (HT) and Graves' disease., Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling, Positive expression of pSTAT3 is associated with poor prognosis in gastric cancer patients.[review; meta-analysis], The present study therefore demonstrated that 2-alkyl substituted quinazolines target the JAK2/STAT3 pathway for their antitumor activity, Activation of c-Src/STAT3 signaling by Ceacam1L is a crucial factor in glioblastoma-initiating cell maintenance and tumorigenesis. Monomers of the cytoplasmic domain of Ceacam1L bound to c-Src and STAT3 and induced their phosphorylation., Study showed low expression level of miR-519d associated with TNM staging and metastasis of breast cancer, and suggested it as a tumor suppressor with role in breast cancer cell proliferation and invasion by downregulating STAT3., Data provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA., BCL-XL up-regulation by STAT3 contributes to mutant KRAS-mediated apoptosis resistance. Such resistance can be overcome by potent BIM induction and concurrent BCL-XL antagonism, RNAi-mediated silencing of Anxa2 inhibits breast cancer cell proliferation by downregulating cyclin D1 in STAT3-dependent pathway., Downregulation of STAT3 phosphorylation enhances tumoricidal effect of IL-15-activated dendritic cell against doxorubicin-resistant lymphoma and leukemia via TNF-alpha., Targeted inhibition of STAT3 combined with gemcitabine enhances in vivo drug delivery and therapeutic response in pancreatic ductal adenocarcinomas., Reduced STAT3-dependent gene transcription underlies low Th-17 responses in GOF-STAT1 CMC, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d, Increased IL10, not IL4 or IL13, in senescent eyes activates STAT3 signalling that induces the alternative activation of macrophages and vascular proliferation., ATR is down-regulated by STAT3-regulated microRNA-383 in A431 cells., suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors, IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment., These data uncover a synthetic lethal interaction involving glutathione production and mitochondrial reactive oxygen species regulation in Ras-transformed cells that is governed by mitochondrial STAT3 and might be exploited therapeutically., STAT3 and miR-21 are cooperative regulators of stemness, migration and tumor initiation in lung-derived brain metastasis, Data suggest the therapeutic potential of microRNA miR-23a/interleulin-8 (IL-8)/Stat3 protein (Stat3) signaling axis in nasopharyngeal carcinoma (NPC). radiosensitization., Silencing Beclin1 in HTLV-1-transformed T cells resulted in diminished activities of NF-kappaB and Stat3 as well as impaired growth., IL-25 upregulated PD-L1 surface expression through the signaling pathways of JNK and STAT3, with STAT3 found to constitutively occupy the proximal region of the PD-L1 promoter., The positive expression rate of STAT3 was higher in breast cancer tissue compared to normal breast tissue, which was correlated with clinical stage, tumor differentiation, and lymph metastasis., Data indicate that box protein 1, high mobility group (HMGB1) could regulate the expression of STAT3 transcription factor by modulation of its DNA methylation in CD4(+) T cells., Applying chromatin immunoprecipitation (ChIP) technique and luciferase assay, we further approved that FoxM1 can transcriptionally active signal transducer and activator of transcription 3 (STAT3), ensuring normal HESC differentiation., high levels of STAT3 correlate with the refractory state at the single-cell level under conditions of both spontaneous and induced lytic activation; importantly, STAT3 also regulates lytic susceptibility., The results of the present study clearly demonstrate that the STAT3 pathway triggered by anti-inflammatory IL-27 plays a role in protecting cardiomyocytes against GSC-mediated damage., These findings underscore the importance of understanding the complex interactions between PR and other regulatory factors, such as Stat3, that contribute to determine the context-dependent transcriptional actions of PR., HES5 knockdown resulted in the reduction of p-STAT3, onstitutive STAT3 phosphorylation in circulating CD4+ T cells is common in recent-onset untreated RA and associates with good treatment response in patients characterized by high disease activity and the presence of systemic inflammation, Placental endothelial cell-derived PDGF-BB recruits human placental multipotent mesenchymal stromal cells involved in vascular development via PDGFR-beta/STAT3 activation, PAFR stimulated EMT by activating STAT3 via upregulation of G-protein-dependent SRC or JAK2 kinase activity. STAT3 transcriptionally elevated PAFR expression. A forward feedback loop between PAFR and STAT3 drives the malignant progression of NSCLC., Increased STAT3 activation during immune responses., IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxo1., The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in salivary adenoid cystic carcinoma specimens., SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-alpha Signaling, GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways, Data show that crizotinib can induce cytoprotective autophagy by suppression of STAT3 transcription factor in lung cancer cells., increased expression in placental endothelial cells associated with pre-eclampsia, data suggest that STAT3 contributes to NK cell recognition by modulating NKG2D ligands in K562/AO2 cells, which may a mechanism by which cells survive and cause relapse of leukemia., MiR-125a suppresses cervical tumor growth, invasion and metastasis by targeting STAT3., by molecular docking analysis and tumor sphere assay we discover that curcumin was able to inhibit JAK2 activity and reduce tumor spheres via inhibiting the JAK2/STAT3 signaling pathway, the present study demonstrated that Fzd2 contributes to the migration and invasion of OSCC cells, at least partly through regulation of the STAT3 pathway, Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection., miR-125a-5p directly targets IL-6R and STAT3 expression in HEK-293T cells., potential utility of a signature involving Bcl-2 overexpression, Rac1 activation and STAT3 phosphorylation for stratifying clinical lymphomas based on disease severity and chemoresistance, in patients with hyper-IgE syndrome, mutations lead to impaired Th17 cell numbers, Letter, SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus, The human monocytes are predisposed to differentiate towards an macrophage activation program characterized by the CD16(+)CD163(+)MerTK(+)pSTAT3(+) phenotype and functional properties such as enhanced protease-dependent motility, and immunomodulation., Our study indicates that apigenin induces apoptosis through inhibition of STAT3 signalling and could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer., These results indicated that the coordinated recruitment of STAT3, CREB-1, and GR to the promoter of the gene encoding COX-2 contributes to the feed-forward induction of COX-2 activity and prostaglandin synthesis in the amnion during parturition., Paeoniflorin induced growth suppression and apoptosis in human glioma cells through the proteasome-dependent degradation of STAT3., Data indicate the role of tropomyosin-related kinase-B (TrkB) in activation of the interleukin-6/Janus kinase 2/STAT3 transcription factor and PI3 kinase/c-AKT proto-oncogene protein pathway in breast cancer., miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of human bronchial epithelial cells, PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3., These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation., MicroRNA-29a promotes apoptosis of monocytes by targeting STAT3 during sepsis, The activation of STAT3 by nuclear PKM2 was associated with gefitinib resistance., data show decreased nuclear accumulation and transcriptional activity of STAT3 in PAK4-silenced pancreatic cancer cells, lack of p21 has catabolic effects by regulation of aggrecan and MMP-13 expression through STAT3 phosphorylation in the cartilage tissue, pimozide reduced the basal expression of phosphorylation STAT3 at tyrosine 705 and reversed the expression of phosphorylation of STAT3 induced by IL-6 addition, suggesting that pimozide can suppress cellular STAT3 activation, these data indicate that IL-6 inhibits starvation-induced autophagy and that p-STAT3 mediates the signal transduction from IL-6 to downstream proteins including Bcl-2 and Beclin1, Our data suggest that miR-21 expression is increased in breast cancer and plays an important role as a tumor gene by targeting STAT3, which may act as a double-response controller in breast cancer., STAT3 linker domain mutants to have profound effects of inhibiting STAT3 transcriptional activation., Blockade of p-STAT3 in combination with conventional chemotherapeutic drugs improves cancer stem cell eradication in head and neck squamous cell carcinoma., This review provides a full spectrum of STAT3's involvement in breast cancer by consolidating the knowledge about its role in breast cancer development, Studies indicate that cadherins mediate cell to cell interactions are potent activators of the signal transducer and activator of transcription 3 (Stat3), thereby offering survival signaling., Antisense oligonucleotide AZD9150 decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models., Data show that signal transducer and activator of transcription-3 (STAT-3) activation occurs downstream of leukotriene B4 receptor-2 (BLT2) and mediates cisplatin resistance in SK-OV-3 cells., Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo, STAT3 inhibition in spheroids generated from the established cancer cells and primary glioblastoma patient-derived cells altered the rounded morphology and increased drug sensitivity., Our results suggest that NFkappaB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney, HSP90 inhibitor ganetespib inhibits pancreatic cancer cell proliferation via JAK2/STAT3 pathway., A novel role of STAT3/miR-21 axis and CDK5/CDK5R1 (p35) in metastasis of head and neck squamous cell carcinoma., Identification of a gain-of-function STAT3 mutation (p.Y640F) in lymphocytic variant hypereosinophilic syndrome., SEA induces cell cross talk-dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis., This study discovered allosteric communications between STAT3 domains., The endometrium of women with dormant genital tuberculosis is associated with poor receptivity, as evidenced by aberrant LIF-STAT3 signaling., Report the interaction between miR-143 and STAT3 prevents cell proliferation/invasion in esophageal squamous cell carcinoma., Ceramide induced the binding of STAT3, but not NF-kappaB or c-Jun, to HAMP promoter. Inhibition of STAT3 with a pan-JAK kinase inhibitor and STAT3 siRNA pool also diminished the induction of both HAMP promoter activity and mRNA expression by ceramide., In conclusion, our data suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer., the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma., HSP72 blocks fibroblast activation and proliferation in renal fibrosis via targeting the STAT3 pathway and may serve as a novel therapeutic agent for chronic kidney disease regardless of the etiology, miR-874 functions as a tumor suppressor by repression of STAT3 in human colorectal cancer cells, The present study finds that the aspirin-FOXD3-OLA1P2-STAT3 axis exhibits exciting anticancer effects and provides new insights into the chemopreventive mechanisms underlying aspirin use, UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways., this study proposes that inflammation-induced Jak-STAT3 signaling leads to colon cancer development through proteasomal degradation of DICER1 by ubiquitin ligase complex of CUL4A(DCAF1), which suggests a novel therapeutic opportunity for colon cancer, found STAT3 could bind promoter region of TXNDC17 (-623 bp to -58 bp relative to the transcription start site (TSS)) for regulating its expression, STAT3 plays an important role in IFN-induced A3G production, and HBsAg may correlated with poor response to IFN treatment,
OMIM_DISEASE Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile-onset,
SP_COMMENT disease:Defects in STAT3 are the cause of hyperimmunoglobulin E recurrent infection syndrome autosomal dominant (AD-HIES) [MIM:147060]; also known as hyper-IgE syndrome or Job syndrome. AD-HIES is a rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eczema, recurrent Staphylococcal infections, increased serum IgE, eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures., function:Transcription factor that binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA., miscellaneous:Involved in the gp130-mediated signaling pathway., online information:STAT3 entry, online information:STAT3 mutation db, PTM:Tyrosine phosphorylated in response to IL-6, IL-11, CNTF, LIF, CSF-1, EGF, PDGF, IFN-alpha and OSM. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity., similarity:Belongs to the transcription factor STAT family., similarity:Contains 1 SH2 domain., subcellular location:Shuttles between the nucleus and the cytoplasm. Constitutive nuclear presence is independent of tyrosine phosphorylation., subunit:Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with NCOA1, PELP1, SOCS7 and STATIP1. Interacts with HCV core protein. Interacts with IL23R in presence of IL23. Interacts with IL31RA. Interacts with SIPAR. Interacts (via SH2 domain) with NLK (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import (By similarity). Interacts with TMF1., tissue specificity:Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.,