Database for Annotation, Visualization and Integrated Discovery 2.1
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cortactin(CTTN) cortactin(CTTN) Related Genes Homo sapiens
GENERIF_SUMMARY substrate for caspase cleavage during apoptosis, Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase, The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in endothelial cells, Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change, at least in part through the regulation of cortactin binding to PAK., cortactin links receptor endocytosis to actin polymerization by binding both CD2AP and the Arp2/3 complex, which may facilitate the trafficking of internalized growth factor receptors, alternative splicing of the F-actin binding domain of cortactin is a new mechanism by which cortactin influences cell migration, cortactin and EC myosin light chain kinase have roles in mediating lung vascular barrier augmentation evoked by S1P, RhoGAP functionally interacts with cortactin and represents a novel determinant in the regulation of cell dynamics., Data suggest that hyaluronan-CD44 interaction with Rac1-protein kinase N gamma plays a pivotal role in phospholipase C gamma1-regulated calcium signaling and cortactin-cytoskeleton function required for keratinocyte cell-cell adhesion and differentiation., HAX-1 binds bile salt export protein (BSEP), cortactin, MDR1, and MDR2. HAX-1 and cortactin regulate BSEP abundance in the apical membrane of cells., Erk phosphorylation liberates the SH3 domain of cortactin from intramolecular interactions with proline-rich regions, causing it to synergize with WASP and N-WASP in activating the Arp2/3 complex, Suppression of cortactin expression with a cortactin antisense oligo significantly impaired S1P-induced capillary formation, migration of endothelial cells, and actin assembly at the cell periphery., a major role for a Crk-cortactin complex in actin polymerization downstream of tyrosine kinase signaling, Overexpression of cortactin may play a role in the metastasis of HCC by influencing cell motility, and cortactin could be a sensitive marker for HCC with intrahepatic metastasis., cortactin can restrict N-WASP localization around EGF-bead-induced protrusions, The p47phox, EMS1 amplification parallels with the progress of oral carcinogenesis., Cortactin promotes cell motility by enhancing lamellipodial persistence, at least in part through regulation of Arp2/3 complex., Cortactin recruitment is dependent on the activation of a phosphoinositide-3-kinase/Rac1-GTPase signalling pathway, which is required for actin polymerization and internalization of N. meningitidis., Our results demonstrated the dominant expression of p85 form of cortactin in colorectal cancer for the first time., cortactin is the crucial gene within the 11q13 amplicon that mediates the invasive potential of human carcinomas, Tyrosine phosphorylation of cortactin by Src family kinases regulates neutrophil transmigration., We describe that S1P-stimulated cortactin translocation to the cell periphery to form lamellipodia is specifically mediated by the endothelial S1P1 G-protein coupled receptor, and is regulated by G(i)-mediated Akt-dependent S1P1 receptor phosphorylation., Co-localization of cortactin and phosphotyrosine identifies invadopodial complexes closely associated with the plasma membrane at active sites of focal degradation of the extracellular matrix in breast cancer cells., Our findings suggest that cortactin plays a role in Listeria internalization, but not in the formation of actin clouds and tails, or in bacteria intracellular motility., Increased levels of cortactin, as found in human carcinomas, promote cell migration and invasion by reducing cell spreading and intercellular adhesive strength., Cortactin is a requirement for pedestal formation and suggest a novel function for the predicted alpha-helical region of cortactin in actin assembly induced by EPEC and EHEC., Results suggest that the AMAP1/cortactin complex, which is not detected in normal mammary epithelial cells, is an excellent drug target for cancer therapeutics., functional importance of cortactin to CD44s-promoted metastasis was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F-B5 and MDA-MB-231 breast cancer cells using RNAi, EMS1 amplification is uncommon and appears to be late event in the development of ethmoid sinus adenocarcinoma., The identification of 17 new sites of phosphorylation in cortactin is reported., Results suggest that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin., Plays important role in CXCR4 signaling and trafficking as well as in receptor-mediated cell migration., Controls osteoclastic bone resorption by regulating actin organization., data suggested potential roles in oral carcinogenesis and that TAOS1 might be involved earlier than EMS1. Both genes might be candidate biomarkers for diagnosis and prognosis in OSCC, Tyrosine phosphorylation of cortactin dynamically links ICAM-1 to the actin cytoskeleton, enabling ICAM-1 to form clusters and facilitate leukocyte transmigration., CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in esophageal squamous cell carcinoma., cortactin-mediated signaling pathways, with emphasis on its contribution to tumor progression and metastasis formation.[REVIEW], These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10., Cortactin binding to EHEC virulence factors, Tir and EspF(u), is dependent upon tyrosine phosphorylation during infection., A major role of cortactin in invadopodia is to regulate the secretion of MMPs and point to a novel mechanism coupling dynamic actin assembly to the secretory machinery, producing enhanced ECM degradation and invasiveness., Higher intensity of cortactin and fascin-1 staining correlated directly with more-advanced cancer stages (TNM) and inversely with survival rates., cortactin and actin have roles in hyperoxia-induced activation of NADPH oxidase and ROS generation in human lung endothelial cells, Cortactin and p120 are shown to directly interact with each other via the cortactin N-terminal region, Using a variety of approaches including siRNA, expression of dominant negative derivatives and pharmacological inhibitors, Results demonstrate the crucial role of cortactin in the activation of the Arp2/3 complex during InlA-mediated entry., in addition to its role in microtubule-dependent cell motility, HDAC6 influences actin-dependent cell motility by altering the acetylation status of cortactin, which, in turn, changes the F-actin binding activity of cortactin, CD44 is an important regulator of HGF/c-Met-mediated in vitro and in vivo barrier enhancement, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin., cortactin-mediated actin remodeling in excitable cells is not only important for cell structure, but may directly impact membrane excitability, tyrosine protein phosphorylation regulates large conductance voltage- and calcium-activated potassium channels via cortactin, EMS1 protein expression is related to the carcinogenesis, lymph node metastasis and clinical stage of gastric carcinoma., potential mechanisms by which cortactin may link vesicular trafficking and dynamic branched actin assembly to regulate protease secretion for invadopodia-associatedextracellular matrix degradation, PTP1B regulates cortactin tyrosine phosphorylation by targeting Tyr446, These results suggest that cortactin hyperphosphorylation suppresses cell migration possibly through the inhibition of membrane localization and tyrosine phosphorylation of p130Cas., many studies have documented a role for cortactin in promoting cell motility and invasion, including a critical role in invadopodia, actin rich-subcellular protrusions associated with degradation of the extracellular matrix by cancer cells., CTTN gene variation may contribute to severe asthma, Overexpression of cortactin is associated with head and neck squamous cell carcinomas, These results imply that cortactin is recruited to the site of EHEC adhesion in vitro and ex vivo by different mechanisms and suggest that cortactin might have a role during EHEC infection of mucosal surfaces., Cortactin, fascin-1 and EGFR have roles in progression of ovarian carcinomas, Overexpression of cortactin is associated with head and neck squamous cell carcinoma., The strong relationship of CTTN amplification/overexpression with prognosis and disease outcome reinforces its role as a driver of 11q13 amplification in HNSCC., Higher cortactin scores positively related to tumor differentiation of esophageal SqCC. Significantly worse prognosis in patients with high scores of cortactin, poor differentiation, T4 stage, positive for lymph node metastasis and distant metastasis., Higher expression of cortactin and survivin significantly correlated with advanced clinicopathological stage in renal cell carcinomas., Higher expression of survivin and cortactin correlates significantly with tumor stages and shorter survival time. Survivin and cortactin may be good biomarkers of aggressiveness of colorectal adenocarcinomas., SFK and cortactin constitute an important signaling pathway that functionally links E-cadherin adhesion and the actin cytoskeleton, HER2 carboxyl-terminal fragments regulate cell migration and cortactin phosphorylation, Results confirm the importance of alterations in CCND1 and CTTN with respect to areca-associated oral squamous cell carcinoma, and demonstrates that there is an early occurrence of amplification of these genes in the risk population., 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., localization of cortactin in cancer cells and interaction between ZO-1 and cortactin are crucial for cancer progression., TocP markedly exerted anti-invasive activities through alteration of cortactin distribution, Our data support a potential role of aberrant cortactin expression in melanoma tumor progression, The quantity and percentage of EMS1 protein expression in laryngeal carcinoma tissues was significantly higher than those in para carcinoma and in normal laryngeal mucosa tissues., Data provide insights into the molecular basis for vascular barrier-regulatory cytoskeletal responses and quantified the critical interactions between non-muscle MLCK isoenzymes and cortactin during vascular barrier regulation., In 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens, cortactin expression was evaluated by immunological analyses, and the correlations of the overexpression of cortactin with clinicopathologic factors were evaluated., CTTN is consistently co-amplified with CCND1 and expressed at higher levels in breast cancers harbouring 11q13 amplification, suggesting that CTTN may also constitute one of the drivers of this amplicon., Protein kinase D controls actin polymerization and cell motility through phosphorylation of cortactin, novel mechanism for regulation of proliferation in 11q13-amplified HNSCC cells, in which overexpressed cortactin acts via RhoA to decrease expression of Cip/Kip CDKIs, and highlight Skp2 as a downstream effector for RhoA in this process, Data show that concurrent phosphorylation of cortactin by ERK1/2 and tyrosine kinases enables cells with the ability to regulate actin dynamics., Our findings suggest a novel mechanism by which an EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion, Cortactin overexpression has been found in many cancer types, including melanomas, ovarian, gastric, hepatic, colorectal and esophageal. (Review), TPM4, PDIA and SRC8 were also localized to the trophoblast cells, further highlighting the importance of these cytoskeletal remodelling proteins in early pregnancy, EMS1 expression was positively related to DcR3, which might play an important role in the carcinogenesis and development of laryngeal carcinoma., Endocytosis in colon cancer cells is dependent on an intact expression of CTTN., cases of squamous cell laryngeal carcinoma with absent to weak expression of CTTN in the deep invasive front showed good prognosis parameters, and a second group with moderate to strong expression of CTTN were associated with an unfavorable prognosis, Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells., Endogenous mature miR-182 expression may have an important role in the pathogenesis of lung cancer through its interference with the target gene CTTN by epigenetic modification., These data suggest that the acetylation status of CTTN modulated by the NACC1-HDAC6 deacetylation system induces acceleration of melanoma cell migration activity via an actin-dependent cellular process, Cortactin and focal adhesion kinase have roles in cancer risk in patients with laryngeal premalignancy, Cortactin interacts with and stimulates the kinase activity of focal adhesion kinase upon Helicobacter pylori infection., Both motility and lamellipodial defects of cortactin-KD cells were fully rescued by plating on increasing concentrations of exogenous extracellular matrix (ECM). Cortactin-KD cell speed defects were not rescued on ECM produced by cortactin-KD cells., Data suggest that GEP100-Arf6-AMAP1-cortactin pathway, activated by VEGFR2, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets., We demonstrated cortactin and MT1-MMP expression in ameloblastoma., Knockdown of cortactin or silent mating type information regulation 2 homolog 1 expression inhibited both migration and invasion of DU145 prostate cancer cells., The cortactin acts as a bridging molecule between actin filaments and focal adhesions., HDAC6 promotes the migration and invasion of bladder cancer cells by targeting the cytoskeletal protein cortactin., Cortactin phosphorylation, local pH increase, and cofilin activation regulates the dynamic cycles of invadopodium protrusion and retraction and is essential for cell invasion in 3D., These results suggest that the actin binding protein cortactin is required for actin stress fiber formation in muscle cells and that this process is absolutely required for translocation of GLUT4-containing vesicles to the plasma membrane., MLCK is essential for the translocation and association of cortactin and p47phox., a complex containing cortactin and RCC2/TD60 complex that may play a functional role in cells undergoing mitosis., Over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis., Strong immunoexpression of cortactin is a predicting factor for increased cancer risk in oral premalignant lesions., Dephosphorylation of FAK upon inhibition of beta integrin resulted in dissociation of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling and induced cell rounding, leading to radiosensitization., A cooperative interplay between FAK, Src and cortactin enables endocytosis of N. meningitidis into host cells., cortactin seems to be a satisfactory marker to predict tumour progression and survival in cases of prostate cancer., Regulation of late endosomal/lysosomal maturation and trafficking by cortactin affects Golgi morphology., overexpression of cortactin and fascin-1 implies poorer tumor differentiation, advanced AJCC stage, and shorter survival rate in pancreatic and ampulla of Vater adenocarcinomas, Cortactin controls surface expression of the voltage-gated potassium channel K(V)10.1., results suggest that SKAP2 negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WAVE2-cortactin complex, Overexpression of cortactin is closely associated with liver embolus and metastasis., Suggest that SIRT1 and cortactin may play a role in the progression of non-small cell lung cancer and may cooperate during tumor progression in NSCLC., Data indicate that luteolin and quercetin attenuate the phosphorylation of cortactin and Src, disruption of invadopodia generation suppression of matrix metalloproteinase MMP9 secretion, and reduction in metastasis., Results suggest that elevated shear stress induces MUC5AC hypersecretion via tyrosine-phosphorylated cortactin-associated actin polymerization in cultured human airway epithelial cells., GIT1-cortactin association through GIT1-Spa homology domain is required for cortactin localization to the leading edge and is essential for endothelial cell directional migration and tumor angiogenesis., Combining cortactin and CTTN mRNA detection with clinicopathologic features improved the predictive power. High expression of both cortactin and CTTN indicated poor survival time of 12 +/- 3.67 months and low expression indicated longer survival time, Data indicate the specific contribution of fascin and cortactin during invadopodium formation., Data suggest that curcumin is an activator of non-receptor type 1 protein tyrosine phosphatase (PTPN1) and can reduce cell motility in colon cancer via dephosphorylation of pTyr(421)-cortactin (CTTN)., Cortactin has a role as a scaffold for Arp2/3 and WAVE2 at the epithelial zonula adherens, Cortactin, another player in the Lyn signaling pathway, is over-expressed and alternatively spliced in leukemic cells from patients with B-cell chronic lymphocytic leukemia., The present study demonstrated that bladder cancer cells with cortactin knockdown have a reduced capacity to extravasate into the lung from the circulation, due to the decreased invasive character of invadopodia., Overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of esophageal squamous cell carcinoma cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001)., c-src-mediated phosphorylation requires RTPAalpha, Cortactin expression promoted the migration, invasion and proliferation of SGC-7901 cells both in vivo and in vitro, association of cortactin with Pfn-1 is regulated by c-Abl-mediated cortactin phosphorylation, These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents., Data suggest a mechanism for the negative regulation of cortactin by FBXL5 protein in gastric cancer cells migration., Two amino acid residues confer different binding affinities of Abelson family kinase SRC homology 2 domains for phosphorylated cortactin., expression of a charge-neutralizing cortactin mutant inhibited contraction and actin dynamics during contractile activation., These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network., Studies show that IQGAP1 functions as a hub linking HGF-induced signaling to microtubules and actin remodeling via EB1-IQGAP1-cortactin interactions., Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR326, thereby relieving the suppressive effect of miR326 on CTTN expression., Upregulation of CTTN is critical for Vascular endothelial growth factor-C- mediated tumor growth and metastasis of esophageal squamous cell carcinoma., Integrated omic analysis of oropharyngeal carcinomas reveals human papillomavirus-dependent regulation of the AP-1 pathway and elevated cortactin protein levels., These results implicate that the role of MTSS1 suppresses cell migration and invasion by inhibiting expression of CTTN and as a prognosis biomarker in Glioblastomas, The cortactin SH3 domain contributes to podosome assembly while fascin actin bundling is a master regulator of podosome disassembly in THP-1 macrophages and dendritic cells., This review focuses on recently published evidence that endothelial ABPs, such as cortactin, myosin, or alpha-actinin, regulate leukocyte extravasation by controlling actin dynamics, biomechanical properties of endothelia, and signaling pathways, Host cortactin, PKD1 and actin are recruited by Trypanosoma cruzi extracellular amastigotes based on experiments in fixed and live cells by time lapse confocal microscopy., Dysregulation of cortactin and HDAC6 is implicated in the invasiveness and migration of prostate cancer cells., Studied the expression of cortactin in HCT116 cells treated with one of the major components of Chansu, Cinobufagin., Findings show CTTN significantly upregulated in colon cancer, while its ectopic expression promotes cell proliferation and tumorigenicity through EGFR-ERK pathway regulation suggesting that CTTN plays an important role in colon cancer progression., cortactin is crucial in invasion and migration of glioma cells, which may promote the migration and invasion of glioma cells by regulating lamellipodia formation, a process requiring the combination of cortactin and the Arp2/3 complex, acetylation-mimicking mutants of alpha-tubulin and cortactin counteract HDAC6-induced ciliary disassembly., The results indicate that cortactin is involved in the regulation of apoptosis induced by VacA in gastric cells., These data suggest a model in which phosphatidylinositol 3,5-bisphosphate binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover., We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology., These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing., Study highlights the potential role of CCM3 in regulating tight junction complex organization and brain endothelial barrier permeability through CCM3-ERK1/2-cortactin cross-talk, the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, findings reveal that Keap1 regulates cell migration by affecting the subcellular localization and activity of cortactin independently of its role in oxidant stress responses.,
SP_COMMENT function:May contribute to the organization of cell structure. The SH3 motif may function as a binding region to cytoskeleton. Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation., online information:Cortactin entry, similarity:Contains 1 SH3 domain., similarity:Contains 7 cortactin repeats., subcellular location:Associated with membrane ruffles and lamellipodia., subunit:Interacts with SHANK2 and SHANK3 via its SH2 domain. Also interacts with FGD1 (By similarity). Interacts with PLXDC2.,
hematopoietic cell-specific Lyn substrate 1(HCLS1) hematopoietic cell-specific Lyn substrate 1(HCLS1) Related Genes Homo sapiens
GENERIF_SUMMARY substrate for caspase cleavage during apoptosis, TBB induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells., found in cell types other than hematopoietic cells, HS1 Tyr phosphorylation catalyzed by Syk and Lyn plays a crucial role in the translocation of the protein to the membrane and is involved in the cytoskeleton rearrangement triggered by thrombin in human platelets, The HS1 coiled-coil region acts synergistically with the repeat domain in the modulation of the Arp2/3 complex-mediated actin polymerization., HS1 may play a role in cytoskeleon organization in B-cells and leukemic B-cells, HS1 is a central regulator of cytoskeleton remodeling that controls lymphocyte trafficking and homing and significantly influences the tissue invasion and infiltration in chronic lymphocytic leukemia., SH3 domain of HS1 protein recognizes lysine-rich polyproline motifs., High HS1 expression predicts poor survival of chronic lymphocytic leukemia patients., a novel role for HS1 and its phosphorylation during neutrophil directed migration., HS1 overexpressed in leukemic as compared to normal B lymphocytes., interaction of HCLS1 with LEF-1 is essential for G-CSF-triggered myeloid differentiation; data demonstrate the importance of HCLS1 in myelopoiesis in vitro and in vivo, Phosphoproteome analyses reveal specific implications of Hcls1, p21-activated kinase 1 and Ezrin in proliferation of a myeloid progenitor cell line downstream of wild-type and ITD mutant Fms-like tyrosine kinase 3 receptors., SDF1alpha-induced interaction of the adapter proteins Nck and HS1 facilitates actin polymerization and migration in T cells.,
SP_COMMENT developmental stage:Expressed in early stage of myeloid and erythroid differentiation., function:Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression., PTM:Phosphorylated by LYN; rapidly after cross-linking of surface IgM on B-cells., similarity:Contains 1 SH3 domain., similarity:Contains 4 cortactin repeats., subunit:Associates with the SH2 and SH3 domains of LCK. Binding to he LCK SH3 domain occurs constitutively, while binding to the LCK SH2 domain occurs only upon TCR stimulation. A similar binding pattern was observed with LYN, but not with FYN in which the FYN SH2 region associates upon TCR stimulation but the FYN SH3 region does not associate regardless of TCR stimulation. Directly associates with HAX1, through binding to its C-terminal region. Interacts with HS1BP3., tissue specificity:Expressed only in tissues and cells of hematopoietic origin.,