Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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Wnt family member 1(WNT1) Wnt family member 1(WNT1) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12q13,
ENSEMBL_GENE_ID ENSG00000125084,
GENERIF_SUMMARY Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells., Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling, The potential role of the WNT-1 gene in basal cell carcinoma seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels., Data show that Wnt-1 induces expression of antiapoptotic genes in 3T3-L1 preadipocytes such as IGF-I and IGF-II, which allows these cells to resist apoptosis in response to serum deprivation., Role of Wnt pathway in medulloblastoma oncogenesis, Wnt signaling has a role in endothelial cell growth control and this is mediated through cell-cell contact, Wnt signal transduction through the Tak1 pathway phosphorylates and inhibits TCF, which might function as a feedback mechanism, CTNNB strongly increased activity of the eN/Nt5 promoter and this increase depended on the presence of TCF-1; demonstrated a link between Wnt signaling and the regulation of eN and ADA, which control the metabolism of adenosine, Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation., Oncogenic activation of the WNT/beta-catenin signaling pathway is common in hepatocellular carcinoma., Causal relationship exists between aberrant Wnt-1 signaling and estrogen receptor+ mammary tumors, HCV core protein induces Huh-7 cell proliferation whether alone or in the context of HCV replication, which is at least partly mediated by transcriptional upregulation of growth-related genes, in particular wnt-1, Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells, Wnt-1, beta-catenin and APC expressions were related to the differentiation of oral squamous cell carcinoma., aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing, hAR is a direct target of LEF-1/TCF transcriptional regulation in PCa cells; expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt, Akt, and PP2A, EGCG blocks Wnt signaling by inducing the HBP1 transcriptional repressor and inhibits aspects of invasive breast cancer, increased Wnt signaling, as achieved by ectopic expression of Wnt-1, triggers the DNA damage response and an ensuing cascade of events resulting in tumorigenic conversion of primary breast epithelial cells, the MED12 interface within Mediator is a new component in the Wnt/beta-catenin pathway, Wnt/beta-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of beta-catenin gene mutations in most tumors, beta-catenin level depends on the way and level of Wnt pathway activation, Wnt signaling activation significantly decreases the viability of retinoblastoma cell lines by inducing cell cycle arrest, which was associated with upregulated p53, sFRP-1, a target gene of the hedgehog pathway, is involved in cross-talk between the hedgehog pathway and the Wnt pathway, The identification of a beta-catenin-T-cell factor-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated epithelial-mesenchymal transition programmes., Wnt/beta-catenin signaling has a role in neurodevelopment as well as in neurodegenerative diseases [review], Wnt1 is critical for protection in the SH-SY5Y neuronal cell line against genomic DNA degradation, membrane phosphatidylserine (PS) exposure, and microglial activation., Wnt1 signaling inhibits interfollicular progenitor cell growth and promotes terminal differentiation of keratinocytes., importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development, Wnt and epidermal growth factor receptor signaling pathways are altered through aberrant methylation and mutation in non small cell lung cancer, vascular Bmp Msx2 Wnt signaling and oxidative stress have roles in arterial calcification [review], Silencing of WNT1 by siRNA induces apoptosis of MCF-7 human breast cancer cells., Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc, Wnt-1 strongly induced the expression of matricellular protein osteopontin, and modestly enhanced the expression of type I collagen in DPSCs. Unexpectedly, Wnt-1 inhibited alkaline phosphatase activity and the formation of mineralized nodules in DPSCs., MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling, direct binding of NF-kappaB-p50 to the Wnt-1 promoter, A positive feedback stimulation of the Wnt pathway by activation of snail., HIF-1alpha was found to inactivate the Wnt signaling by binding to hARD1 or beta-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells., the Wnt/beta-catenin pathway contributes to carcinogenesis and cancer cell survival by driving expression of OPG, In the gastric cancerous tissues, the expression percentage of Wnt-1, beta-catenin and E-cadherin is 54.4%, 45.6%, 47.2%, respectively, which is significantly higher than the percentage expression of these genes in normal tissues (p<0.01)., RCK/ p54 might be a determinant of colorectal cancer proliferation by activating the canonical Wnt pathway, HDAC3 overexpression alters the epigenetic programming of colon cancer cells to impact intracellular Wnt signaling and their sensitivity to external growth regulation by vitamin D, The Wnt1 overexpression is associated with the expression of tumour-associated Wnt-targets, tumour proliferation, angiogenesis and a poor prognosis in NSCLCs., ER stress causes dissociation between GRP78/BiP and Wnt, an interaction essential for its correct posttranslational processing, propose that cytoplasmic stabilization of beta-catenin through palmitoylation of Wnt-1 and subsequent activation of the pathway is a potential mechanism of FASN oncogenicity in prostate cancer, adenomatous polyposis coli gene and nuclear b-catenin may have roles in wnt-related progression of invasive urothelial carcinomas, Dpr1 negatively modulates the basal activity of Wnt1/beta-catenin signaling in the nucleus by keeping LEF1 in the repressive state., analysis of Wnt/beta-catenin and Myc signaling in liver cancer, WNT1 was overexpressed in ovarian carcinoma, Wnt1 and Wnt signaling have an important role in human mesenchymal stem cell osteogenesis., the 3' untranslated regions of WNT1 and JAG1 were functional targets of miR-34a and miR-21 and provide evidence that these targets were translationally suppressed, Activation of Wnt/beta-catenin signalling pathway induces chemoresistance to IFN-alpha/5-FU therapy., Wnt/beta-catenin signaling pathway may be activated abnormally in some nasopharyngeal carcinoma (NPC) patients. beta-catenin may be a prognostic factor of NPC., WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth, Ectopic expression of either Wnt1 or stabilized beta-catenin in vitro induced the transcription factor Snail and suppressed nephrin expression, leading to podocyte dysfunction, CDK5-splicing variant might also be a negative regulator of Wnt/beta-catenin signaling pathway., PPP(S/T)P motif phosphorylation of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity, HMGA1 is involved in proliferation and gastric tumor formation via the Wnt/beta-catenin pathway., These data demonstrate that mesenchymal stem cells from mice and humans produce Wnt proteins and TGF-beta1 that respectively stimulate lung fibroblast proliferation and matrix production., Activated embryonal development-related wnt1/beta-catenin pathway might take part in the oncogenesis and growth of neural crest-derived neuroblastoma., Results suggest that the blockade of Wnt-1-mediated signaling may offer a potential pathway-specific therapeutic strategy for the treatment of a subgroup of HCC that over-expresses Wnt-1., SALL4 plays a critical role in the pathogenesis of MDS by causing the aberrant activation of the Wnt/beta-catenin pathway., procaine and procainamide reactivate WIF-1 in lung cancer cells and downregulate the Wnt canonical pathway, the beta-catenin-dependent Wnt pathway is integrated with integrin signaling through the adaptor molecule Grb2, Mutations in the human naked cuticle homolog NKD1 found in colorectal cancer alter Wnt/Dvl/beta-catenin signaling, activation of the Wnt pathway is associated with high proliferation, dedifferentiation and a solid morphology in biliary tract cancer, the WIF-1 gene is frequently down-regulated or silenced in astrocytomas by aberrant promoter methylation, Overexpression of Wnt1/beta-catenin might predict the clinicopathologic stage and prognosis of esophageal squamous cell carcinoma (ESCC) and the level of Wnt1/beta-catenin mRNA was conversely correlated with lymph node metastasis and advanced disease., Data indicate involvement of canonical Wnt signaling and link between the Wnt pathway and chromatin regulation in epithelial stem cells., Intratumoral Wnt1 overexpression could produce more aggressive NSCLCs by induction of survivin., The protein expression levels of Wnt1, beta-catenin and Cyclin D1 were all positively correlated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grades of patients with gliomas., Wnt-1 regulates IL-1beta-mediated HIF-1alpha induction via NF-kappaB., TMEM88 associates with Dvl proteins and regulates Wnt signaling in a context-dependent manner, the aim of this study was to investigate the prognosis and clinicopathologic roles of beta-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in esophageal squamous cell carcinoma, Novel insights into roles for DKK1 in addition to canonical WNT signaling and the mechanism of colon cancer initiating cells transformation., These findings demonstrate that Wnt1 is a novel angiogenic protein that is expressed in developing endothelial cells and can be therapeutically deployed to increase blood flow and angiogenesis., High Wnt1 is associated with non-small cell lung cancer after surgery., WNT1 and SFRP1 mRNA levels were higher in DU145 cells compared to non-osteotropic cells., PDE5 inhibition by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/beta-catenin-mediated transcription in human breast tumor cells, Abnormal expression of E-cadherin, beta-catenin, Wnt-1 was observed., BR-DIM and CDF inhibited the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network, leading to the inactivation of Wnt signaling consistent with inhibition of prostate cancer cell invasion, Data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/beta-catenin signaling in certain colon cancer cells., Interplay of Wnt and c-MYC signaling during intestinal homeostasis and transformation., Data suggest that VDR controls the level of nuclear beta-catenin in colon cancer cells and can therefore attenuate the impact of oncogenic mutations that activate the Wnt/beta-catenin pathway., a connection between Wnt1 signaling and the transcriptional regulation of neurodegenerative disease genes, One mechanism through which canonical Wnt signaling could shape niches supportive of hematopoiesis., Studies indicate that pathways of Hedgehog (Hh), Wnt and Notch, which regulate development during embryonic life and somatic stem cells (SCs) in the adult organism, can be reactivated in malignancies and support tumor-initiating cells (TIC) scompartment., Data indicate that CDH11 as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin signaling, with frequent epigenetic inactivation in common carcinomas., Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires beta-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways., Epigenetic silencing of sFRP1 activates the canonical Wnt pathway and contributes to increased cell growth and proliferation in hepatocellular carcinoma, Erythropoietin prevents beta-amyloid degeneration of microglia via Wnt1/PI 3-K/mTOR/Bad/Bcl-xL pathway., This study establishes an association between low Wnt-1 and high Dkk-1 serum levels and premature myocardial infarction, Wnt/beta-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4, Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival Wnt/beta-catenin signaling, GSK3beta plays an essential role in Ras degradation and inhibition of this degradation pathway by aberrant Wnt/beta-catenin signaling may contribute to Ras-induced transformation in colorectal tumorigenesis, Studies idicate that NOTCH, BMP4 and WNT pathways are involved in the regulation of intestinal cancer stem cells., peptide derived from the loop 2 region of sclerostin blocked the interaction of sclerostin with LRP5/6 and also inhibited Wnt1 but not Wnt3A or Wnt9B signaling. This suggests that these Wnts interact with LRP6 in different ways, R-Spondin potentiates Wnt/beta-catenin signaling through orphan receptors LGR4 and LGR5, These results suggest, for the first time, that the Wnt/beta-catenin pathway regulates ABCB1 in CML., PDZ-RGS3 can enhance signals generated by the Wnt canonical pathway and plays a pivotal role in epithelial mesenchymal transition, Findings suggest that Mel-18 is a novel negative regulator of breast cancer stem cell (CSC) that inhibits the stem cell population and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling., Psychiatric disorder-related behavioral abnormalities are displayed in a neural crest-derived brain region of WNT1/GAL4 double-transgenic mice., Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein, Promoter hypermethylation of WNT gene is associated with Basal Cell Carcinoma., Studies indicate that DISC1 and AKT were invlved in the regulation of GSK3beta and Wnt signaling paathway., Mutations in WNT1 are a cause of osteogenesis imperfecta., Mutations in WNT1 cause different forms of bone fragility., WNT1 mutations are associated with moderately severe and progressive recessive osteogenesis imperfecta., Wnt1 expression in invasive breast tumour cells seems to promote differentiation and apoptosis, while being related inversely to proliferation., Data indicate that the canonical Wnt/sscatenin signaling pathway appears to trigger amniotic fluid mesenchymal stem cells (huAFMSC) osteoblastogenesis., The Wnt1-beta-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancer stem cell expansion., This report identifies human skeletal diseases associated with mutations in WNT1., alterations of the Wnt1/beta-catenin axis in clear cell renal cell carcinoma (ccRCC) were examined., Wnt-1 is a target of regulation by miR-200b and miR-22., High WNT1 expression is associated with prostate cancer., A functional missense variant of WNT1 (rs61758378 resulting in S88R)was overrepresented in autism spectrum disorder patients. Functional analysis revealed that WNT1-S88R is more active than wild-type WNT1 in assays for the Wnt/beta-catenin signaling pathway., In human pancreatic mucinous cystic neoplasms, expression of Wnt1 was detected in focal cyst epithelial cells in the majority of cases. The ovarian-like stroma was diffusely positive for Wnt1 in all of the human MCN cases examined., Hypoxic macrophages impair autophagy in epithelial cells through Wnt1., FGFR1, WNT, and TGF-beta have roles in signaling of reactive stroma in aggressive prostate adenocarcinomas, Identify emilin2 as a key extracellular regulator of the Wnt signalling pathway suppressing breast cancer cell growth and migration., These findings provide important evidence that the reduced miR-152 expression by HCV core protein can indirectly lose an inhibitory effect on Wnt1, which might, at least partially lead to cell proliferation of liver cancer cells., Upregulation of WNT1 is associated with lung cancer invasion., Activation of Wnt1 and beta-catenin signaling accelerates the proliferation of gastric cancer stem cells., WNT/beta-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer., The expression levels of WNT1 was found to increase in both cancer stem cells and non- cancer stem cells when cancer stem cells were maintained as spheroids, Data indicate that BMVC- and BMVC4-repressed WNT1 gene expression through stabilizing the G-quadruplex structure formed at its promoter., Data indicate that miR-122 suppressed the activation of Wnt/beta-catenin pathway by targeting WNT1., Bisphosphonate treatment of children with WNT1 mutations was associated with increasing lumbar spine areal bone mineral density z-scores, but the effect was smaller than what had been reported for children with classical osteogenesis imperfecta., The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests, Results suggest ivermectin as therapeutic WNT protein-TCF transcription factor pathway response blocker to treat WNT-TCF-dependent diseases including multiple cancers., Our study suggests that Sox9 siRNA inhibits the proliferation capability of human osteosarcoma cells by down-regulating the expression of Wnt1 and its receptor Fzd1, Paracrine WNT signaling is stimulated by estrogen and progesterone, while autocrine WNT signaling is induced by the embryonic T-box transcription factor TBX3, in the absence of retinoid signaling via RARbeta, reduced IGF-1 signaling results in suppression of epithelial-mesenchymal transition and delays tumorigenesis induced by the Wnt1 oncogene, Wnt1 stimulates osteogenic differentiation and mineralization of human periodontal ligament fibroblasts, mainly by activating the canonical Wnt/beta-catenin pathway, in which Runx2 is a key downstream regulator., WNT1 was a direct target of miR-148b, and overexpressed WNT1 inversely correlated with miR-148b levels in hepatocellular carcinoma tissues., Agonists of epoxyeicosatrienoic acids reduce infarct size and ameliorate cardiac dysfunction via activation of HO-1 and Wnt1 canonical pathway., Wnt1 promotes CD36 expression via activation of PPAR-gamma and TCF4., Data suggest that fibulin-5 functions as a metastasis suppressor in lung cancer by modulating tumor microenvironment to suppress Wnt/beta-catenin signaling., Results suggested that Wnt1-induced MAFK expression promoted cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might be closely linked to the Wnt signaling pathway., Suggest that TGF-beta1/Smad and Wnt/CTNNB1 signaling pathways both contribute to pathological scar formation., MCF7 cells over-expressing both WNT1 and FGF3 show a 3.5-fold increase in mammosphere formation; conditioned media from these cells also promotes stem cell activity in untransfected parental MCF7 and T47D cells, as WNT1 and FGF3 are secreted factors., IWR-1 has the potential to suppress tumor metastasis by inhibiting Wnt/beta-catenin pathway as well as survivin expression, High expression of WNT1 is associated with liver cancer., Studies indicate crosstalk between Notch receptor and Wnt protein, Hedgehog protein, hypoxia and transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) pathways.,
OMIM_DISEASE Osteogenesis imperfecta, type XV, Osteoporosis, early-onset, susceptibility to, autosomal dominant,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule important in CNS development. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3.,
Wnt family member 10A(WNT10A) Wnt family member 10A(WNT10A) Related Genes Homo sapiens
CHROMOSOME 2,
CYTOBAND 2q35,
ENSEMBL_GENE_ID ENSG00000135925,
GENERIF_SUMMARY c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in an autosomal recessive ectodermal dysplasia, mantle cell lymphoma highly and consistently expressed Wnt3 and Wnt10., The first inherited missense mutation in WNT10A with associated ectodermal features, is reported., Study reports on 12 patients, from 11 unrelated families, with ectodermal dysplasia caused by five previously undescribed WNT10A mutations, Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism), Mutations in the WNT10A gene are associated with ectodermal dysplasia presenting as palmoplantar keratoderma in two families., WNT10A may be a novel angio/stromagenic growth factor, Case Reports, We observed a marginally significant interaction between WNT10 rs10177996 (intron 1) and an individual's proportion of calories from saturated fat., In a panel of 34 patients with isolated hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2 have been sequenced. WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia., WNT10A acts as an autocrine oncogene both in renal cell carcinoma carcinogenesis and progression by activating WNT/beta-catenin signaling., the expression level of Wnt10a is higher in endometrioid carcinoma than in non-endometrioid subtypes; however, the underlying mechanism remains unclear., Nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) Polish patients with non-syndromic tooth agenesis., Expression studies in human hair follicle tissue suggests that WNT10A has a functional role in androgenetic alopecia etiology., Mutations in WNT10A are frequently involved in oligodontia associated with minor signs of ectodermal dysplasia., WNT10A variants were associated with non-syndromic tooth agenesis from mild to severe tooth agenesis, and the more severe tooth agenesis, the stronger association., Our study has demonstrated for the first time that agenesis of the maxillary permanent canines is a distinct entity, associated with mutations in WNT10A., WNT10A and EDA digenic mutations could result in oligodontia and syndromic tooth agenesis in the Chinese population. Moreover, our results will greatly expand the genotypic spectrum of tooth agenesis., WNT10A mutations account for (1/4) of population-based isolated oligodontia and show phenotypic correlations., Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A., involvement of PAX9, EDA, SPRY2, SPRY4, and WNT10A as risk factors for MLIA. uncovered 3 strong synergistic interactions between MLIA liability and MSX1-TGFA, AXIN2-TGFA, and SPRY2-SPRY4 gene pairs. 1st evidence of sprouty genes in MLIA susceptibility., Patients with bi-allelic WNT10A mutations have severe tooth agenesis., The novel c.-14_7delinsC mutation might be the etiological variant of the WNT10A gene responsible for the permanent tooth agenesis in the Egyptian family., transmission disequilibrium test showed transmitted disequilibrium in C392T. we found an association between the C392T variant and nonsyndromic oral clefts., WNT10A may induce kidney fibrosis and associate with kidney dysfunction in acute interstitial nephritis., WNT10A promotes the proliferation of DPCs and negatively regulates their odontoblastic differentiation., p.Arg113Cys, p.Phe228Ile, newly identified p.Arg171Leu may represent aetiological mutations underlying MLIA w/associated dental anomalies, implicating coding variants in WNT10A gene, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages., High WNT10A expression promotes an invasive and self-renewing phenotype in esophageal squamous cell carcinoma, WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness,
OMIM_DISEASE Tooth agenesis, selective, 4, Schopf-Schulz-Passarge syndrome, Odontoonychodermal dysplasia,
SP_COMMENT disease:Defects in WNT10A are the cause of odonto-onycho-dermal dysplasia (OODD) [MIM:257980]. OODD is a rare autosomal recessive ectodermal dysplasia in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin., function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule important in CNS development. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family.,
Wnt family member 10B(WNT10B) Wnt family member 10B(WNT10B) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12q13,
ENSEMBL_GENE_ID ENSG00000169884,
GENERIF_SUMMARY pyrethroid insecticides and estrogen can enhance the expression of the WNT10B proto-oncogene, mutations represent the first naturally occurring missense variants of WNT10B, suggest that fibroblast growth factor switches WNT10B from a negative to a positive cell growth regulator, Metastatic osteosarcoma cell lines showed better chemotaxis response to Wnt10B than the non-metastatic osteosarcoma cell lines, By homozygosity mapping a novel Split-Hand/Foot Malformation locus at 12q13.11-q13 with a maximum multipoint lod score of 5.47; by subsequent candidate gene approach a homozygous missense WNT10b mutation was identified., This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry., In Wnt10b-expressing mammary tumors, levels of p27(KIP1) were extremely low; conversely, Wnt10b-null mammary cells expressed high levels of this protein, suggesting Wnt-dependent regulation of p27(KIP1)., S1P induces osteoblast precursor recruitment and promotes mature cell survival. Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation., We have not found evidence for a robust association of common WNT10B gene allelic variants with either BMD or fractures in postmenopausal women., This study is the first report of the association of common genetic polymorphism of WNT10B with human fat accumulation., Homozygous nonsense mutation in WNT10B is associated with sporadic split-hand/foot malformation with autosomal recessive inheritance., Wnt10b, but not Wnt3a, stimulates the NFkappaB and Notch pathways in U2OS osteosarcoma cells., A novel sequence variant (c.986C>G, p.Thr329Arg) of WNT10B has been identified in familial split-hand/foot malformations in a large consanguineous Pakistani family., Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition, common variation in WNT10B was shown to be associated with BMI and weight in a case-control population of Belgian males., we identified WNT10B as a direct target of miR-148a in cancer-associated fibroblasts from endometrial cancers, Variations in WNT10B do not contribute to human monogenic obesity in our population., Results suggest that Wnt10b likely plays an important role in the development of endometrial cancer (EC). The results also identify a role for Wnt10b in EC cells through promoting proliferation and inhibiting apoptosis., WNT10B/beta-catenin signalling induces HMGA2 and proliferation in metastatic breast cancer tumours devoid of ERalpha, PR and HER2 expression., No association between WNT10B polymorphisms and adiposity parameters was found. However, a role for WNT10B variants in determining human bone mineral density was found., Hypoxia-inducible factor-2alpha-dependent hypoxic induction of Wnt10b expression in adipogenic cells., Sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation., these findings clearly demonstrate that Wnt10b promotes epidermal keratinocyte transformation through induced Egf pathway, Data show that Wnt protein Wnt10b is expressed in cardiomyocytes and localized in the intercalated discs of mouse and human hearts., WNT10B enhances proliferation through beta-catenin and RAC1 GTPase in human corneal endothelial cells.,
OMIM_DISEASE Split-hand/foot malformation 6,
SP_COMMENT developmental stage:Infant brain has higher levels of WNT10B than adult brain., function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., tissue specificity:Detected in most adult tissues. Highest levels were found in heart and skeletal muscle. Low levels are found in brain.,
Wnt family member 11(WNT11) Wnt family member 11(WNT11) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11q13.5,
ENSEMBL_GENE_ID ENSG00000085741,
GENERIF_SUMMARY WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma. Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway., Wnt11 stimulates proliferation, migration, cytoskeletal rearrangement, and contact-independent growth by a beta-catenin-independent mechanism, Wnt11 promotes cardiac differentiation via the non-canonical PKC-dependent signaling pathway, Wnt11 gene is expressed during early embryonic development and has a critical role in regulation of gastrulation movements., Wnt5a and Wnt11 expression in EPC cells was induced by coculture with rat neonatal cardiomyocyte and was blocked by gamma-secretase inhibition., Wnt-11 promotes cell viability and is involved in coordination of key signaling pathways., Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs., These observations suggest a novel role for Wnt11 as a tumor suppressor during hepatocarcinogenesis because loss of expression promotes the malignant phenotype via both canonical and noncanonical Wnt signaling pathways., These observations suggest that the increased level of Wnt-11 found in prostate cancer contributes to tumour progression by promoting neuroendocrine-like differentiation., Data provide evidence for an autocrine regulatory loop involving transcriptional upregulation of WNT11 by ERRalpha and beta-cat that influences the migratory capacity of cancer cells., WNT11 emerged as a direct target of ERG., These observations highlight the distinct roles of WNT11 and WNT4 during the early stages of retinoic acid-induced neuronal differentiation., Wnt11 is involved in the protection of the host intestinal cells by blocking the invasion of pathogenic bacteria, suppressing inflammation, and inhibiting apoptosis., Wnt11 mRNA expression was significantly higher in the stage I, II, III, or IV colorectal tumor tissues than in non-tumor colon., Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent, Data established a seven-gene (AR, ESR2, GATA3, GBX2, KRT16, MMP28 and WNT11) prognostic signature to define a subset of triple-negative breast cancer (TNBC)., Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues., differential Wnt11 immunoexpression in high-grade human serous ovarian cancer compared to low-grade human serous ovarian cancer could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels., High expression of Wnt-11 is associated with metastasis in cervical cancer., Report high expression of Wnt11 in esophageal squamous cell carcinoma, which was significantly associated with AJCC stage., Demonstrate immunohistochemical expression of Wnt11 and BCL2A1 in complete moles and normal villi.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., tissue specificity:Expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas.,
Wnt family member 16(WNT16) Wnt family member 16(WNT16) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q31,
ENSEMBL_GENE_ID ENSG00000002745,
GENERIF_SUMMARY genomic analysis of conserved sequences between human, rat, and zebrafish WNT16, Targeted-Wnt16b inhibition leads to apoptotic cell death, and Wnt16b mediates its effect through canonical Wnt pathway involving dishevelled-2, beta-catenin and survivin; Wnt16 plays an important role in leukemogenesis., Targeted-E2A-PBX1 inhibition leads to reduced expression of the EB-1 and Wnt16b genes; aberrant expression of these genes may be a key step in leukemogenesis in t(1;19)-positive pre-B leukemia., Wnt16 does not activate canonical Wnt signaling in E2A-PBX1-positive cells. Instead, beta-catenin is involved in N-cadherin-dependent adherence junctions, Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., study identified WNT16B as a new marker of senescence that regulates p53 activity and the PI3K/AKT pathway and is necessary for the onset of replicative senescence, these findings postulate that the WNT16/C7orf58 locus contains complex patterns of genetic variation, which play an important role in peak bone mass accrual and may likely impact BMD determination at later life., These results suggest a critical role of Wnt 16 signaling pathway on cortical bone thickness and bone strength determination as well as fracture susceptibility., Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B., Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97, Common missense polymorphisms of the WNT16 gene are associated with bone mineral density at the hip, calcaneal ultrasound and the buckling ratio of the femoral neck, as well as with hip fractures in individuals under 80 years of age., results suggest synergistic effects of WNT16a insertion and the at-risk 'T' allele of TCF7L2 (rs7903146) for elevating the expression of TCF7L2 in human pancreas which may affect the regulation of downstream target genes involved in the development of T2D, Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues., Increased translation of WNT16 can thus lead to an increased inhibitory action of WNT16 on canonical WNT signaling., variants at WNT16 were more strongly related to upper limb-bone mineral density, than to bone mineral density at the other sites., Osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility., Describe TGFbeta-Wnt16-Notch signaling conduit in the chondrocyte-like transformation of VSMCs and identify endogenous TGFbeta activity in MGP-null VSMCs as a critical mediator of chondrogenesis., MicroRNA-374b Suppresses Proliferation and Promotes Apoptosis in T-cell Lymphoblastic Lymphoma by Repressing AKT1 and Wnt-16, ALL cells expressing WNT16 are sensitive to endoplasmic reticulum stress, and show enhanced killing after addition of chloroquine., Data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure. WNT16-TG mice exhibited significantly higher whole-body areal bone mineral density and bone mineral content., loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., tissue specificity:Isoform Wnt-16b is expressed in peripheral lymphoid organs such as spleen, appendix, and lymph nodes, in kidney but not in bone marrow. Isoform Wnt-16a is expressed at significant levels only in the pancreas.,
Wnt family member 2(WNT2) Wnt family member 2(WNT2) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q31.2,
ENSEMBL_GENE_ID ENSG00000105989,
GENERIF_SUMMARY Up-regulation of WNT2 mRNA by estrogen might play a key role in some cases of human breast cancer through activation of the beta-catenin - TCF signaling pathway., Activating mutations of the WNT2 gene are not a major contributor to the development of autistic disorder., REVIEW, Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism., Target genes involved in tumor WNT pathways in response to TGF-beta1 were found in cervix cancer cells., Wnt/beta-catenin signalling pathway is activated in most of gastric cancers, which may play pivotal roles either in gastric cancer formation or in tumour invasion and dissemination, Inhibition of Wnt2 by monoclonal antibodies is of therapeutic interest in the development of more effective treatments for malignnt pleueral mesothelioma., The increased Wnt2 expression in gastric cancers is paralleled with reduction of membranous E-cadherin., The WNT2 gene is upregulated along the progression from low-grade dysplasia to esophageal adenocarcioma., Regulation of Fz4 expression by Wnt2., inhibition of both Wnt-2 and Gal-3 had synergistic effects on suppressing canonical Wnt signaling and inducing apoptosis, suggesting that aberrant canonical Wnt/beta-catenin signaling in colorectal cancer can be regulated at multiple levels, 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., Persistent upregulation in colorectal carcinoma cases studied., Wnt (Wnt2), Stat3, and Notch-1 and -2 signaling are correlated in human epidermal tumors., Knockdown of Wnt2 by siRNA in human U251 glioma cells inhibited cell proliferation and invasive ability, and induced apoptotic cell death, The results suggest that WNT2 could act through its receptor FZD9 to regulate the beta-CATENIN pathway in cumulus cells, recruiting beta-CATENIN into plasma membranes and promoting the formation of adherens junctions involving CDH1., up-regulation of the Wnt-2 protein might play a role in the development of colorectal cancers., RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance., Wnt2 acts as an angiogenic factor for non-sinusoidal endothelium in vitro and in vivo., These data demonstrate that mesenchymal stem cells from mice and humans produce Wnt proteins and TGF-beta1 that respectively stimulate lung fibroblast proliferation and matrix production., Wnt2/beta-catenin signaling pathway is constitutively activated in esophageal squamous cell carcinoma (ESCC) cells, indicating that Wnt2/beta-catenin pathway plays an essential role in carcinogenesis of the esophagus., findings provide evidence for a significant association between WNT2 and autism., The present study does not support a major role for WNT2 in schizophrenia., DNA methylation within the WNT2 promoter in human placenta is associated with low birthweight., a haplotype of WNT2 (rs2896218-rs6950765, Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition, significant association with SNP rs4730775 locus on chromosome 7 with genetic susceptibility to Peyronie's disease, The WNT2 gene may play a suggestive role in language development in autistic disorder., Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo., Pdgf signaling potentiates Wnt2-Wnt7b signaling to promote high levels of Wnt activity in mesenchymal progenitors that is required for proper development of endoderm-derived organs, such as the lung, The skin lesions of scleroderma patients showed obviously increased expression of cytoplasmic Wnt 2, nuclear Wnt 3a and beta-catenin, but markedly lowered cell membrane expression of beta-catenin than normal skin., Decreased placental expression of Wnt2 and increased placental expression of sFRP4 may be associated with the pathogenesis of severe preeclampsia., The study demonistrated that expressions of Wnt-2 in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67., Hypermethylation of WNT2 is associated with colorectal cancer., We demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in non-small cell lung cancer cells, High expression of Wnt2 is associated with pancreatic cancer progression promoted by pancreatic stellate cells., Wnt2/beta-catenin signaling was involved in stromal-epithelial cells interaction in endometriosis., Wnt2 complements Wnt/beta-catenin signaling in regulating colorectal cancer cell proliferation.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., tissue specificity:Expressed in brain in the thalamus, in fetal and adult lung and in placenta.,
Wnt family member 2B(WNT2B) Wnt family member 2B(WNT2B) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p13,
ENSEMBL_GENE_ID ENSG00000134245,
GENERIF_SUMMARY This is the first report on differential regulation of WNT2 and WNT2B mRNAs in human cancer cell lines., Wnt-2b mRNA is expressed in human ovarian cancer cells, REVIEW, in addition to alternative promoters and RNA splicing, an alternative translation start in Wnt13B and Wnt13C mRNAs increases the complexity of both human wnt13 expression and functions, Heplipin induced KG-1 cell apoptosis is related with Wntl3 and ATPase3., Hedgehog signals and bHLH transcription factors are involved in WNT2B upregulation, which is counteracted by BMP, WNT and Notch signals., High Wnt2B overexpression is associated with ovarian cancer metastasis and drug resistance., secretion of WNT2B and WNT9B and stabilization of beta-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism, these results indicate that the high-expression levels of Gli1 and Wnt2B might play a pivotal role during tumorigenesis of pancreatic cancer, Results showed that miR-185-3p contributs to radioresistance of nasopharyngeal carcinoma via modulation of WNT2B expression., ACSL5 mediates antiproliferative activities via Wnt2B palmitoylation with diminished Wnt activity. The molecular pathway is probably relevant for intestinal homeostasis, overwhelmed by other pathways in carcinogenesis., the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters. May be involved in normal development or differentiation as well as in carcinogenesis., similarity:Belongs to the Wnt family., tissue specificity:Isoform 1 is expressed in adult heart, brain, placenta, lung, prostate, testis, ovary, small intestine and colon. In the adult brain, it is mainly found in the caudate nucleus, subthalamic nucleus and thalamus. Also detected in fetal brain, lung and kidney. Isoform 2 is expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis and cancer cell lines.,
Wnt family member 3(WNT3) Wnt family member 3(WNT3) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q21,
ENSEMBL_GENE_ID ENSG00000108379,
GENERIF_SUMMARY Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45, Wnt3 plays an important role in regulating characteristics and activity of stromal cells., The Wnt-3a triggers the interaction of LRP6 with caveolin and promotes recruitment of Axin to LRP6 phosphorylated by glycogen synthase kinase-3beta and that caveolin thereby inhibits the binding of beta-catenin to Axin., an internally truncated LRP5 receptor is strongly implicated in deregulated activation of the WNT/beta-catenin signaling pathway in hyperparathyroid tumors, The results indicated that HBx induction in the CCL13-HBx stable cell line downregulated Wnt-3/beta-catenin expression and suppressed cell growth by repressing cell proliferation or triggering cell apoptosis., a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/beta-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis., CTLA-4 is a direct target of Wnt/beta-catenin signaling and is expressed in human melanoma tumors, WNT3 regulates distinct internalization pathways of LRP6 to tune the activation of beta catenin signaling., mantle cell lymphoma highly and consistently expressed Wnt3 and Wnt10., WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity., RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance., Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., Abnormalities of the Wnt3/3a pathway (located in the apical ectodermal ridge) include tetra-amelia and loss of the distal phalanges/nails., Individuals carrying variant alleles in WNT3 presented an increased risk for cleft lip/palate (p = 0.0003; OR, 1.61; 95% CI, 1.29-2.02) in the Brazilian population studied., Extracellular domain of FZD7 (sFZD7) was tested for its functional activity to interact with Wnt3, its ability to inhibit Wnt3-mediated signaling., SNP rs415430 in the WNT3 gene was not associated with the risk of development of Parkinson disease, The apoptotic index was significantly lower in high-Wnt3 tumors than in low-Wnt3 tumors (P=0.0245)., The findings of a significant association between lip and/or palate clefts and two markers in the WNT3 and COL11A2 genes were the most consistent and were observed in all groups analysed and stratified., study confirmed the involvement of polymorphisms in the WNT3 gene in NCL/P aetiology in the tested population., Knockdown of Wnt3 by siRNA restored cytoplasmic expression of beta-catenin., mRNA level of WNT3 in hESCs correlates with their definitive ectoderm differentiation efficiency., Colorectal tumors express elevated levels of Wnt3 and GPR177., WNT3 inhibits cerebellar granule neuron progenitor proliferation and medulloblastoma formation via MAPK activation., WNT3 and WNT5B are critical factors, secreted from mesenchymal cancer cells, for instigating the epithelial cancer cell invasion., Data show that the WNT/beta-CATENIN signaling cascade components, including WNT ligands WNT3 and WNT5A, is crucial for early odontogenesis., Genome association study shows a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B in patients with classic bladder exstrophy., WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish, WNT3 and membrane-associated beta-catenin regulate trophectoderm lineage differentiation in human blastocysts., Two SNPs (rs3809857 and rs9890413) in the WNT3 gene were subjected to case-control and case-parent analysis,
OMIM_DISEASE Tetra-amelia syndrome,
SP_COMMENT disease:Defects in WNT3 are the cause of autosomal recessive tetra-amelia [MIM:273395]. Tetra-amelia is a rare human genetic disorder characterized by complete absence of all four limbs and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects., function:Ligand for members of the frizzled family of seven transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN.,
Wnt family member 3A(WNT3A) Wnt family member 3A(WNT3A) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1q42,
ENSEMBL_GENE_ID ENSG00000154342,
GENERIF_SUMMARY Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45, Clustered with WNT14 on 1q42., wnt3a-beta catenin signaling regulates LEF-1 gene expression, CKI epsilon-dependent phosphorylation of Dvl enhances the formation of a complex of Dvl-1 with Frat-1 and this complex leads to the activation of Wnt-3a-induced accumulation of beta-catenin, These results suggest that Wnt responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells., Results suggest that disabled-2 functions as a negative regulator of canonical Wnt signaling by stabilizing the beta-catenin degradation complex., Wnt3a may stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon, Wnt/beta-catenin pathway activation by Wnt3a raised beta-catenin in monocytes & decreased migration thru a dermal microvascular endothelial cell layer. This was associated with specific monocyte adherence to endothelial cells after Wnt3a exposure., BMP-2 antagonizes Wnt-3a signaling in osteoblast progenitors by promoting an interaction between Smad1 and Dvl-1 that restricts beta-catenin activation, ILK activity can modulate acute Wnt3a mediated beta-catenin phosphorylation, stabilization and nuclear activation in a PI3K-independent manner., Wnt-LRP5 signalling may play a role in the adaptation of bone to mechanical load in humans, and may explain some gender-related differences in bone mass, Over-expression of the Wnt3a gene significantly enhances the ability of fibroblast feeder cells to support the undifferentiated growth of 3 different human embryonic stem cell lines., Wnt3A/5A can function as mesenchymal regulatory factors by providing instructive cues for the recruitment, maintenance, and differentiation of mesenchymal stem cells., Wnt3A treatment significantly activated human hepatic stellate cells, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells., These results suggest that Wnt signaling crosstalk and functional antagonism with the LRP5 co-receptor are key signaling regulators of mesenchymal stem cells maintenance and differentiation., Blockade of Wnt3a stimulation of IP(5) generation blocks beta-catenin accumulation, Results identify a novel feedback mechanism by which Wnt, including Wnt3a, negatively regulates LRP6 at the mRNA level., These findings demonstrate a requirement of Wnt signaling for maintenance, proliferation, and survival of NP when cultured in neurosphere conditions., Wnt3a markedly reduced the forskolin-induced expression of RANKL, a target gene of PTH/cAMP/PKA., Our results suggest that Wnt/beta-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis., bone marrow sera from 21 multiple myeloma patients significantly suppressed Wnt3a-induced OPG expression and enhanced RANKL expression in osteoblasts in a DKK1-dependent manner, effect of Wnt3a on bone disease and growth of multiple myeloma cells in vitro and in vivo, study demonstrated that Wnt3a & Wnt5a can promote proliferation of HEK293 cells & inhibit serum starvation-induced apoptosis, which implies Wnt3a & Wnt5a can maintain survival of HEK293 cells under stress, FGF antagonizes Wnt signaling by inhibiting Wnt-induced transcription and suggest that multiple mechanisms, including downregulation of TCFs and Wnt receptors, contribute to this effect., glutamine synthetase has a role in control of glutamate signalling through Wnt3A and steroid pathways in osteoblastic cells, both Wnt5a and Wnt3a bound Ror2, only Wnt5a induced Ror2 homo-dimerization and tyrosine phosphorylation in U2OS human osteoblastic cells., Wnt3a and Wnt5a have roles in inducing BMP-4 and 6 expression in prostate cancer osteoblast differentiation, essential role of Wnt3a in hepatocyte differentiation from hESCs; Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation, the frequent loss of stromal TGF-beta type II receptor expression in prostate cancer can relieve the paracrine suppression of Wnt3a expression, These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/beta-catenin signaling in normal melanocyte development., Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs., The presence of WNT3a completely prevents normal adipocyte differentaiton., Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration., Data show that mutated GPC3 lacking the GPI anchoring domain (sGPC3) significantly inhibited the in vivo growth, blocked Wnt signaling and Erk1/2 and Akt phosphorylation in tumors., Wnt3A treatment greatly enhanced the effect of LRP6 on T-cell factor/lymphoid enhance factor luciferase activity in human mammary epithelial cells, Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors., Data demonstrate that the Wnt-beta-catenin signaling pathway is functional in platelets, and that a Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation., Wnt/beta-catenin pathway activation might upregulate DIXDC1 through a post-translational mechanism by inhibiting the ubiquitin-mediated degradation of the DIXDC1 protein., analysis of the frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6, Loss of CYLD instigates tumor growth in human cylindromatosis through a mechanism in which hyperubiquitination of polymerized Dvl drives enhancement of Wnt3/beta-catenin responses., Studies indicate that understanding the contributions of Notch, Wnt and HH signaling to the development of hematopoiesis is critical for achieving successful ex vivo expansion and differentiation of hematopoietic stem cells hematopoietic stem cells., EP2 is a novel transcriptional target of Wnt3a in dermal papilla cells of human scalp hair follicles, up-regulation of DPAGT1 transcripts by Wnt3a led to altered N-glycosylation of E-cadherin., These results support sFRP2's role as an enhancer of Wnt3A/beta-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis., Wnt-3a increases neurogenesis during the differentiation of ReNcell VM cells. Neurogenesis induced by Wnt-3a is independent of the transcriptional activity of Wnt/beta-catenin pathway in ReNcell VM cells., two SNPs of Wnt3A (rs752107 and rs3121310) are significantly associated with NSCLP in Chinese population. These findings provide a context for understanding the genetic aetiology of NSCLP., Forced expression of C4ST-1 in L-Wnt-3a cells inhibited diffusion of Wnt-3a due to structural alterations in CS chains mediated by C4ST-1., These results provide strong evidence that the centrosomal localization of CK1delta is required for Wnt-3a-dependent neuritogenesis., WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways, The genetic variants of WNT3A gene may not be associated with the susceptibility to congenital scoliosis in a Chinese Han population., Results indicate that CK1 isoforms work coordinately to promote the full response to Wnt3a stimulus., In HEK293T cells with intact Wnt signaling, Rac1b is tethered to these same gene promoters independent of Wnt3A stimulation and is further observed to recruit Dishevelled and beta-catenin in the absence of Wnt3A stimulation., when released from E-cadherin by Wnt3a-stimulated phosphorylation, p120-catenin controls the activity of Kaiso, enhancing its binding to repressed promoters and relieving its inhibition of the beta-catenin-Tcf-4 transcriptional complex., Recombinant Sox17 prevents Wnt3a from repressing myelin protein expression, while inhibition of Sox17-mediated proteasomal degradation of beta-catenin blocks myelin protein induction., Wnt3a signalling is upregulated in keloid fibroblasts and this promotes cellular growth, migration and extracellular matrix production in such fibroblasts., HCV core protein enhances Wnt/beta-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis, Combining BMP4/WNT3A induction and OCT4/EpCAM selection can significantly increase the putative germ cell population with meiotic competency., Growth inhibition of magnolol against human colon cancer cells can be partly attributed to the regulation of the Wnt3a/beta-catenin signaling pathway., WNT-3a as a novel upstream regulator of small GTPase activity in platelets, Studies indicate he role of Wnt3a in osteoarthritis (OA)has been well investigated as its activity is reduced in OA., WNT3A putatively associates with primary osteoporosis., CPE forms a complex, probably through sequences located at its N-terminal domain, with Wnt3a and the extracellular cysteine rich domain of Fz1., Wnt3a can induce epithelial-mesenchymal transition, migration, and proliferation of human lens epithelial cells, and may be a valuable therapeutic target for the prevention and treatment of posterior capsular opacification., overexpression of Wnt signaling pathway is associated with malignant breast cancer., During cell differentiation Wnt3a regulates Nkx2.5 and inhibits cardiomyogenesis., human bronchial epithelial cells are able to undergo epithelial-mesenchymal transition in vitro upon nicotine stimulation via the Wnt3a/beta-catenin signaling pathway., The skin lesions of scleroderma patients showed obviously increased expression of cytoplasmic Wnt 2, nuclear Wnt 3a and beta-catenin, but markedly lowered cell membrane expression of beta-catenin than normal skin., WNT3A promoted MSC proliferation via the ss-catenin-mediated canonical Wnt pathway, and inhibited chondrogenesis of mesenchymal stem cells via the calcium/calmodulin-dependent kinase II (CaMKII)-mediated non-canonical Wnt pathway., Wnt3a mediates activation of Wnt/beta-catenin signaling and promotes tumorigenesis and tumor growth in experimental glioblastoma., results indicate that SCN-iPS cells provide a useful disease model for SCN, and the activation of the Wnt3a/beta-catenin pathway may offer a novel therapy for SCN with ELANE mutation, Wnt-induced dishevelled 2 phosphorylation has effects in in canonical and noncanonical Wnt3a and Wnt5a signaling, site-specific Dvl2 phosphorylation is required for Dvl2 association with PKCiota; this interaction is likely to be one of the mechanisms essential for Wnt3a-dependent neurite outgrowth, In ankylosing spondylitis patients, Wnt-3a serum levels are lower in the high activity group compared to low activity group and controls., Paracrine Wnt signaling both promotes and inhibits human breast tumor growth., a new role for Ror2 in conveying a tonic signal to stabilize soluble beta-catenin and create a poised state of enhanced responsiveness to Wnt3a exogenous signals in RCC., The activation of effector T cells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients., Data suggest that activation of Wnt signaling pathway in rhabdomyosarcoma via Wnt3a involves reduced phosphorylation of CTNNB1 (catenin beta-1), stabilization of active cytosolic CTNNB1, and nuclear translocation of CTNNB1., WNT3A alone was a poor inducer of mesoderm from hESCs in defined medium. WNT3A and BMP4 synergized to accelerate mesoderm formation. Added later, WNT3A blocked hematopoiesis and generated mesenchymal colonies., High Wnt3A expression is associated with metastasis in triple negative breast cancer., Data show that beta-arrestins regulate Wnt3a-induced low density lipoprotein receptor-related protein 6 (Lrp6) phosphorylation by the regulation of the membrane dynamics of Amer1., Wnt3a inhibited the apoptosis of mouse embryonic liver stem cells, results demonstrate that, while ER signaling acts synergistically with Wnt3A in promoting osteogenic differentiation, Wnt3A may crosstalk with ER signaling by up-regulating ERalpha expression and down-regulating ERbeta expression in MPCs., Negative modulation of cilia assembly and trafficking by IFT88 siRNA increases canonical wnt signaling in response to wnt3a., these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway., Wnt3a expression is high in the tumor environment; the protein is found in over 50% of primary tumors, but the prevalence is lower in tissue from colorectal cancer metastatic sites., SNP rs752107 in WNT3A was strongly associated with decreased total hip BMD showing the highest significance under the recessive model, Application of recombinant Wnt3a showed an anti-proliferative effect on keratinocytes in a dose-dependent manner., WNT3A gene expression is associated with isolated Hirschsprung disease polymorphism and disease status., Mutation of any individual cysteine of Wnt3a results in covalent Wnt oligomers through ectopic intermolecular disulfide bond formation and diminishes/abolishes Wnt signaling., Wnt3a recruits the Wnt-calcium signaling pathway in peripheral nerves in a pain model., The LRP6 tyrosine mutant increased in signaling activation in response to Wnt3a/beta-catenin stimulation., p66(Shc) plays a vital part in canonical Wnt signaling in the endothelium and mediates Wnt3a-stimulated endothelial oxidative stress and dysfunction., miR-195 is key in regulating cell proliferation, cell cycle and apoptosis through targeting Wnt3a., High WNT3A expression is associated with glioblastoma., High WNT3A expression is associated with bone destruction in lung and breast cancer., The interaction between Wnt isoforms and their LRP6 cognate receptor depends on the jutting loop present in Wnt3a but absent in Wnt5b., Wnt3a expression was associated with epithelial mesenchymal transition and promoted colon cancer progression., a Wnt-amplified environment was associated with superior pulp healing., Wnt3a and Notch3 may promote the metastasis of non-small cell lung cancer and Notch3 upregulation is required for the Wnt3a mediated increased metastatic abilities of non-small cell lung cancer., These observations demonstrated the first time that Wnt3a can directly activate MyoD expression through targeting cis-elements in the DE and the L fragment., Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation., Wnt3a can modulate intracellular localisation and secretion of sFRP4., 72 Wnt target genes higher expressed in triple-negative breast cancer, Upregulated Wnt3a in colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin., The results reveal a novel inhibitory role of Wnt3a on canonical Wnt/beta-catenin signaling and cancer cell proliferation when there is an insufficient blood supply during tumor development., The pool of ADP-ribosylated Axin, which is degraded under basal conditions, increases immediately following Wnt stimulation in both Drosophila and human cells.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN., tissue specificity:Moderately expressed in placenta and at low levels in adult lung, spleen, and prostate.,
Wnt family member 4(WNT4) Wnt family member 4(WNT4) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p36.23-p35.1,
ENSEMBL_GENE_ID ENSG00000162552,
GENERIF_SUMMARY WNT-4 protein is expressed in the developing nephron during morphogenetic period of the kidney., Down-regulation of Wnt-4 and up-regulation of Wnt-5a are possible markers of the malignant phenotype of human squamous cell carcinoma., overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy, matrilysin may have a role in renal tubular injury and progression of tubulointerstitial fibrosis, and Wnt4 may regulate matrilysin expression in the kidney, Their different spatial expression patterns suggest that Wnt4 and Wnt5a proteins are not functionally linked to type II collagen and type X collagen synthesis in in vitro chondrogenic models of mesenchyme stem cells, sequencing of all five exons of WNT-4 demonstrated no mutant alleles in any of 8 46,XX true hermaphrodites. The possibility of the existence of causative mutations in the untranslated regions of WNT-4, or within introns cannot be ruled out., It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter., Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes, These data show that DKK3 and WNT4 have multiple actions on steroidogenesis in adrenocortical cells, including effects on overall steroidogenesis (aldosterone and cortisol biosynthesis) and distinct effects on steroidogenic enzyme mRNA levels., The activation of p38 was dependent on Axin and was required for the enhancement of mesenchymal stem cells differentiation by Wnt-4., Molecular analysis of the WNT4 gene in 6 patients with Mayer-Rokitansky-Kuster-Hauser syndrome without androgen excess excluded this gene as a major cause of this syndrome, regardless of the subtype., Together with previous observations in animal models, the present data attribute a pivotal role to WNT4 signaling during organogenesis in humans., WNT4 is involved in the regulation of mullerian duct development and ovarian androgen biosynthesis. WNT4 may also contribute to human follicle development and/or maintenance., Wnt4 gene, a member of the Wnt-beta-catenin pathway, was identified as a target gene of MM-1., The abundant WNT-4 mRNA expression in Conn's adenomas and its hormonal regulation in adrenocortical cells suggest a role for WNT-4 in human adrenocortical function., These results suggested that activation of Wnt4/Fzd6 signaling through a "beta-catenin-independent" pathway played a role in proliferation and survival of the pituitary adenoma cells., Mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome., RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance., Wnt 4a gene encodes a growth factor that participates in the formation of the kidney, adrenal, mammary gland, pituitary, and female reproductive tract. Wnt4 is required for the initial steps of the formation of Mullerian ducts., Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., The current results support a view that WNT4 may have a role in oocyte selection and follicle formation and maturation in human ovaries., at least 1 cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a loss of function mutation of the Wnt4 (wingless-type MMTV integration site family member 4) gene., Findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo., The age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2alpha expression, was investigated in thymic epithelial cells., Wnt4 is specifically involved in joint development., These observations highlight the distinct roles of WNT11 and WNT4 during the early stages of retinoic acid-induced neuronal differentiation., Report a new WNT4 gene mutation in atypical Mayer-Rokitansky-Kuster-Hauser syndrome., Possible role of WNT4 in Han Chinese women with premature ovarian failure., Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition, Mutations in WNT4 are not responsible for Mullerian duct abnormalities in Chinese women., Mutations in the WNT4 gene is not associated with premature ovarian failure., Recent developments have demonstrated that ovarian development is an active process (rather than a default process); ovarian development/function requires expression of WNT4, RSPO1, and FOXL2. [REVIEW], We confirm WNT4, CDKN2BAS and FN1 as the first identified common loci for endometriosis., Studies uncovered a linear pathway involving BMP2, WNT4/beta-catenin, and Forkhead box protein O1 that operates in human endometrium to critically control decidualization., Analysis of bronchial biopsy samples shows a very strong correlation between Wnt4 and interleukin (IL)8 gene expression, suggesting a role for Wnt4 in chronic lung inflammation., heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia., State anxiety assessed two months before the examination was positively and negatively correlated with miR-16 and its target WNT4 mRNA levels, respectively., These data indicate that Wnt4 signaling is deregulated in most pituitary adenomas and its excessive activation may inhibit pituitary tumor invasion., The WNT4 ligand plays a role in regulating the cell growth of leukemia-derived cells by arresting cells in the G1 cell cycle phase., We report an adolescent girl with the cardinal features of MURCS association, obesity, and clinical findings of hyperandrogenism who did not show any exonic mutation of the WNT4 gene, Our results suggest that the rs10965235 SNP in the CDKN2B-AS gene and the rs16826658 SNP near the WNT4 gene were significantly associated with endometriosis in this Korean population., The 5'-flanking region of the Wnt4 gene is responsive to Pax8. Pax8 modulates the expression of Wnt4 in thyroid cells., Wnt4 might be a key gene during parathyroid hormone-induced epithelial mesenchymal transformation of proximal kidney tubule cells., The results demonstrated that WNT4 rs2235529 is associated with endometriosis in Chinese Han women, which may result in aberrant expression of WNT4, leading to the pathogenesis of endometriosis., the expression of WNT4, a Wnt ligand, and three targets of Wnt-ss-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples, were investigated., Polymorphisms on WNT4 gene might be involved in the pathogenesis of endometriosis in the infertile women.,
OMIM_DISEASE Mullerian aplasia and hyperandrogenism, SERKAL syndrome,
SP_COMMENT disease:Defects in WNT4 are a cause of Rokitansky-Kuster-Hauser syndrome (RKH syndrome) [MIM:277000]; also called Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH syndrome or MRKH anomaly). RKH syndrome is characterized by utero-vaginal atresia in otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total Muellerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5'000 newborn girls., disease:Defects in WNT4 are the cause of female sex reversal with dysgenesis of kidneys, adrenals, and lungs (SERKAL) [MIM:611812]; also known as SERKAL syndrome., function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity). Overexpression may be associated with abnormal proliferation in human breast tissue., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN.,
Wnt family member 5A(WNT5A) Wnt family member 5A(WNT5A) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p21-p14,
ENSEMBL_GENE_ID ENSG00000114251,
GENERIF_SUMMARY Frequent up-regulation of WNT5A mRNA in primary gastric cancer., Increased expression of WNT5a is associated with cell motility and invasion of metastatic melanoma, WNT5a is upregulated by TNF-alpha in tumor cell lines, Wnt-5a promotes T cell nuclear accumulation of the transcription factor NFAT in the presence of cyclosporin A., These results suggest that the TAK1-NLK MAPK cascade is activated by the noncanonical Wnt-5a/Ca(2+) pathway and antagonizes canonical Wnt/beta-catenin signaling., Results suggest that disabled-2 functions as a negative regulator of canonical Wnt signaling by stabilizing the beta-catenin degradation complex., Down-regulation of Wnt-4 and up-regulation of Wnt-5a are possible markers of the malignant phenotype of human squamous cell carcinoma., Altered mRNA expression is associated with prostate cancer recurrence., Their different spatial expression patterns suggest that Wnt4 and Wnt5a proteins are not functionally linked to type II collagen and type X collagen synthesis in in vitro chondrogenic models of mesenchyme stem cells, Wnt-5a is involved in the response of malignant neuroblasts to retinoic acid., Wnt-5a serves as an antagonist to the canonical Wnt-signaling pathway with tumor suppressor activity in differentiated thyroid carcinomas., Over-expression of Wnt5a in transgenic mice disrupts epithelial-response to FGF10 and regulates Shh signaling., function of Wnt 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions, The role of Wnt5A in the microenvironment of primary breast cancer and macrophage-induced breast cancer invasion., WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-gamma production by mycobacterial antigen-stimulated T cells, NFAT1, a transcription factor connected with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway., The Embryonic Lethal Abnormal Vision-like protein HuR, inhibited translation of Wnt-5a when bound to highly conserved AU-rich sequences in the 3'-untranslated region of the Wnt-5a mRNA., The aberrant expression of WNT5A suggest that the Wnt signaling pathway may be abnormally regulated in nasopharyngeal carcinoma (NPC), which provides insight into the molecular mechanisms of NPC., Screening for Wnt5a-regulated genes in cultured endothelial cells identified several encoding angiogenic regulators, including matrix metalloproteinase-1, an interstitial collagenase, and Tie-2, a receptor for angiopoietins., WNT5A is an important target of CUTL1 and mediator of invasiveness and tumor progression in pancreatic cancer., Wnt5A can signal via protein kinase C (PKC), so the role of PKC in Wnt5A-mediated motility and epithelial to mesenchymal transition was also assessed using PKC inhibition and activation studies, Wnt3A/5A can function as mesenchymal regulatory factors by providing instructive cues for the recruitment, maintenance, and differentiation of mesenchymal stem cells., Our findings demonstrate that APC status plays a key role as a determinant of Wnt5a secretion and suggest that CaSR-mediated secretion of Wnt5a will inhibit defective Wnt signaling in APC-truncated cells in an autocrine manner., Hypomethylation of wingless-related MMTV integration site 5A (WNT5A), S100 calcium-binding protein P (S100P) and cysteine-rich protein 1(CRIP1) was confirmed in the cancer cells by bisulfite sequencing., Ability of phenylmethimazole (C10) to decrease growth and migration of papillary thyroid cancer cells may be related to its suppressive effect on TLR3 and Wnt5a signaling., These results suggest that Wnt signaling crosstalk and functional antagonism with the LRP5 co-receptor are key signaling regulators of mesenchymal stem cells maintenance and differentiation., Data indicate that Wnt5a signaling is an important regulator in the proliferation of glioma cells., did not detect submicroscopic deletion or duplication nor sequence alteration in either CACNA2D3 or WNT5A in ZLS-affected individuals, Review about the different influences and signaling pathways of Wnt5A in tumor progression., The genesis of myelocytic leukemia is related to the down-regulated expression of Wnt5a., Wnt5a and Wnt11 expression in EPC cells was induced by coculture with rat neonatal cardiomyocyte and was blocked by gamma-secretase inhibition., Our findings suggest non-canonical Wnt signalling plays a role in regulating endothelial cell growth and possibly in angiogenesis., These data show activation of the Wnt/beta-catenin-signalling pathway in uveal melanoma and suggest that components of this pathway might be useful prognostic markers as well as attractive therapeutic targets to treat this disease., WNT5A, a putative tumour suppressor gene in ALL, is silenced by methylation in this disease and that this epigenetic event is associated with upregulation of CYCLIN D1 expression and confers poor prognosis in patients with ALL., WNT5A is frequently inactivated in CRC by tumor-specific methylation, and thus, is a potential biomarker., MT1-MMP-induced phenotypic changes were dependent upon up-regulation of Wnt5a, which has been implicated in epithelial-to-mesenchymal transition., Wnt5A is critically involved in inflammatory macrophage signaling in sepsis and is a target for antiinflammatory mediators like APC or antagonists like sFRP1., findings show cell-autonomous mechanisms allow Wnt5a to control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients, Wnt5a expressed in atherosclerotic lesions colocalizes with TLR-4., study demonstrated that Wnt3a & Wnt5a can promote proliferation of HEK293 cells & inhibit serum starvation-induced apoptosis, which implies Wnt3a & Wnt5a can maintain survival of HEK293 cells under stress, negative correlation between expression of Wnt-5a & hepatitis B virus x gene(HBx) mutations in hepatocellular carcinoma(HCC); it is concluded that HBx mutants may participate in development & progression of HCC, at least in part through the Wnt-5a pathway, No mutation found in Zimmermann-Laband syndrome, both Wnt5a and Wnt3a bound Ror2, only Wnt5a induced Ror2 homo-dimerization and tyrosine phosphorylation in U2OS human osteoblastic cells., Wnt3a and Wnt5a have roles in inducing BMP-4 and 6 expression in prostate cancer osteoblast differentiation, Data show that Wnt5a is highly expressed during osteoblastic differentiation, and that clusters of genes regulating cell cycle, cell proliferation and cell growth, and gene transcription are altered with absence of Wnt5a expression., Expression of Wnt5a plasmid but not Wnt1 or Wnt3a increased caudal homeodomain factor CDX2 transcripts and protein in HT-29 adenocarcinoma cells. Wnt5a increased activity of a sucrase-isomaltase (SI) promoter in Caco-2BBE cells., Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome., LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation., WNT5A is regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis, These data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation., Amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression., Staining of a melanoma tissue array also highlighted the inverse relationship between MART-1 and Wnt5A expression., pathways related to Wnt5a have an important role in ovarian malignant neoplasia., Mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome., Wnt5A activates calpain-1, leading to the cleavage of filamin A, which results in a remodeling of the cytoskeleton and an increase in melanoma cell motility, Data show that Wnt-5a stimulation of breast epithelial cells leads to increased cell-cell adhesion, and that Wnt-5a/casein kinase Ialpha (CKIalpha)-specific phosphorylation of beta-catenin leads to increased complex formation of beta-catenin/E-cadherin., WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis., Wnt5a regulates epidermal differentiation even in adult skin, Expression of Wnt-5a protein significantly stimulated cell proliferation, and transfection with siRNA plasmids suppressed Wnt-5 expression and cell proliferation, may be an important marker during initial events of actinic cheilitis malignant transformation; might recruit other events in lip squamous cell carcinoma, such as matrix metalloproteinase 3 synthesis, Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta, Wnt5A is a critical mediator of CXCL12-CXCR4 signaling and migration in human and murine T, Results indicate that Wnt5a/Ror2 signaling involves the activation of a SFK, leading to MMP-13 expression, and that constitutively active Wnt5a/Ror2 signaling confers invasive properties on osteosarcoma cells in a cell-autonomous manner., Laminin gamma2 mediates Wnt5a-induced invasion of gastric cancer cells., Phospho-DARPP-32 potentiates Wnt-5a-mediated CREB activity and suppresses filopodia formation., syndecan 1 and 4 correlate to increased metastatic potential in melanoma patients and are an important component of the Wnt5A autocrine signaling loop, WNT5A gene has been methylated from the early stages of colorectal cancers., Data show that ROR2 knockdown results in a decrease in signaling downstream of Wnt5A., Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines., WNT5A, a putative tumor suppressor gene in acute myeloid leukemia (AML), is silenced by methylation in this disease and that this epigenetic event is associated with upregulation of CYCLIN D1 expression., WNT5A negatively regulates both proliferation and migration of HDPCs, suggesting its important role in odontogenesis via controlling the HDPCs., Wnt5a activated Rac in the beta-catenin-independent pathway, and Frizzled2 (Fz2) and Ror1 or Ror2 were required for this action., A WNT5A/ROR2 signal transduction pathway is important in craniofacial and skeletal development and proper formation and growth of these structures is sensitive to variations in WNT5A function., Data show that tumor spheroid cells express ABCG2, Bmi1, WNT5A, CD133, prox1 and VEGFR3., cGMP-phosphodiesterase 6 can be activated by another cancer-retina antigen, transducin, through Wnt5a-Frizzled-2 cascade, which leads to a lowering of cGMP and an increase in intracellular calcium mobilization., Wnt-5a regulates proliferation in lung cancer cells, WNT5A signaling is important in modulating tumorigenic behaviors of enamel epithelium cells in ameloblastomas., WNT-5a is necessary to maintain osteogenic potential of MSC and inhibition of WNT-5a signaling therefore plays a role in their determination into preadipocytes in humans, Wnt5A is not involved in the onset or progression of MCC and support other data that indicate that Wnt signaling is inactive in this cancer despite its neuroendocrine origins., Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy., study suggest a shift away from canonical Wnt signaling toward noncanonical pathways driven by interactions between Wnt-5a and its cognate receptors in psoriasis, accompanied by impaired homeostatic inhibition of Wnt signaling by WIF-1 and dickkopf, stimulator of adipose tissue-derived mesenchymal stromal cells osteogenic differentiation, A quantitative analysis of the expression of Wnt5A protein in human tissue arrays, containing 600 prostate tissue cores, showed >50% increase in malignant compared to benign cores (p<0.0001)., expressions of mineralization-related genes, Data show that expression of Wnt5a in atherosclerosis and rheumatoid arthritis but not in normal tissue, supporting the role of Wnt5a as an inflammatory mediator in vivo., Data show that epigenetic disruption of WNT5A would contribute directly to the aberrant activation of WNT/beta-catenin signaling during ESCC pathogenesis., Data found that Wnt5a reduces cell surface levels and promotes ubiquitination and degradation of SDC4., In melanoma cells, expressions of Wnt5A and Klotho are inversely correlated., Results suggest that Wnt5a plays the role of a tumor suppressor in leukemogenesis through the Wnt5a/Ror2 noncanonical signaling pathway that inhibits Wnt canonical signaling., Hypermethylation of WNT5a is associated with colon cancer., WNT5A can act as a suppressor factor in leukemogenesis and can be used as a potential marker for curative effect assessment in leukaemia., Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration., PIK3CA mutation and the Wnt pathway have roles in ERalpha-positive breast cancer, Wnt5a plays an important role in regulating chemosensitivity to anticancer drugs in ovarian cancer cells, Data indicate that macrophages alter adipogenesis of 3T3-L1 cells not only via classical proinflammatory cytokines, but also via wnt signalling molecules., Results show expression of Wnt5a and Ror2 is induced during Snail-mediated epithelial-mesenchymal transition or malignant progression of cancer cells and that activated Wnt5a-Ror2 signaling confers highly motile and invasive properties on cancer cells., Several members of the WNT pathway, including WNT5A, FZD5, and DKK1 were highly up-regulated in PCa tissue from patients with advanced PCa., The loss of Wnt-5 may indicate the invasiveness of extramammary Paget's disease., The expression of Wnt5A is significantly increased in chronic rhinosinusitis with nasal polyps compared with controls., Wnt5a plays an important role in human hindgut and anorectal morphogenesis., Wnt5a was prominently expressed in human primary cytotrophoblast cells, but absent in the human choriocarcinoma cell line JAR., Wnt5a methylation was strongly associated with tumour microsatellite instability tumours after adjustment for age, sex, and tumour location, The expression of Wnt5a in the termina1 rectum decreases in children with anorectal malformation (ARM), suggesting Wnt5a may play an important role in the development of ARM., loss of Wnt5a predicts poor outcome in Epithelial ovarian cancer patients and Wnt5a suppresses the growth of cancer cells by triggering cellular senescence, GPC6 promotes invasive migration by inhibition of canonical beta-catenin and Wnt signalling, and up-regulation of non-canonical Wnt5A signalling leading to the activation of JNK and p38 MAPK., under high levels of Wnt5a monocytes could differentiate into unconventional dendritic cells with tolerogenic features., Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b, finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer, Data suggest that an anti-Wnt5a antibody was capable of suppressing Wnt5a-dependent internalization of Fz2 receptor, resulting in the prevention of metastasis of gastric cancer cells by inhibiting the activation of Rac1 and the expression of laminin gamma2., Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-kappaB-B cell lymphoma 6 signaling., Wnt5a-Ror2 signaling might also be required for expression of MMP-13 gene during the development of the cartilaginous tissue., study underlines the critical role of BMSC-derived WNT5A in the regulation of inflammatory processes and suggests its participation in the pathogenesis of rheumatoid arthritis, WNT-5a and ROR2 were more highly expressed in more severe disease states, and therefore may play a coordinated role in the occurrence and progression of osteosarcoma, Wnt5a signalling contributes to tissue invasion by non-melanoma skin cancer, Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects, Modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process., Data suggest that Wnt5a and Ror2 may serve as tumor suppressor genes in the development of hepatocellular carcinoma, and may serve as clinicopathologic biomarkers for prognosis in HCC patients., Under proinflammatory conditions the noncanonical Wnt protein Wnt5a induces immunosuppressive macrophages from malignant epithelial cells and in association with tumor-associated macrophages., Identification of a novel Wnt5a-CK1varepsilon-Dvl2-Plk1-mediated primary cilia disassembly pathway., Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA., Wnt-5a and CYR61 are enriched in the extracellular matrix of liver fibrotic tissue compared with control matrix., High wnt5a expression is involved in the pathophysiology of Multiple myeloma-induced bone disease., These results suggest that Wnt5a signaling positions ESCRT-III in the midbody properly for abscission by stabilizing midbody microtubules, EBV-positive gastric carcinoma had no or very low expression of WNT5A but a high level of methylation in the promoter region., Data indicate that Wnt5a promoters, A and B, are differentially regulated and a model for complex transcriptional regulation of Wnt5a., findings suggest that epithelium-derived SFRP5 may play a probable defensive role in impeding gastric cancer progression, characteristically by inhibiting GEC migration induced by macrophage-derived Wnt5a via JNK signaling activation, Data indicate that Wnt5a mRNA level was correlated positively with CXCR4 mRNA level in Ewing sarcoma (ES) specimens., Wnt5a, APC and beta-catenin genes might be involved in the carcinogenesis and development of colorectal adenocarcinoma. It is hypothesized that down-regulation of APC and Wnt5a proteins may be one of causes of ectopic expression of beta-catenin in CRC., WNT5A was more frequently methylated in early stage gastric carcinomas., WNT-5A signaling is activated by and necessary for TGF-beta-induced extracellular matrix production by airway smooth muscle cells, determined if mutations in WNT5A contributed to the etiology of Mullerian duct abnormalities in 189 Chinese women, Wnt5a may be potentially involved in the effects of inflammation on bone formation., Data indicate changed ecpression levels of PRM2, HSP90 and WNT5A in male of couples experiencing idiopathic recurrent miscarriages., This study demonstrated the first attempt to identify Wnt5a and Ror2 as additional mechanisms contributing to dysregulation of the non-canonical WNT signaling pathway in medulloblastoma. Ror2 may play a role as an oncosuppressor in medulloblastoma., Wnt5a can be used as a predictive biomarker, and favoring the view of Wnt5a as a future therapeutic target in prostate cancer patients with tumor cells displaying low expression of Wnt5a., crucial role of Wnt5a in the smoking-related lung carcinogenesis, Wnt5a promotes breast cancer cell migration via the Dvl2/Rab35/Rac1 signaling pathway., Both WNT5A and NFATc2 proteins are highly expressed in human pancreatic cancer tissues., Wnt-induced dishevelled 2 phosphorylation has effects in in canonical and noncanonical Wnt3a and Wnt5a signaling, Loss of WNT5A expression due to methylation is related to aggressiveness of sporadic breast cancer., ARF6 may provide a means of inhibiting WNT/beta-catenin signaling in cancer, Our results do not support the relevance of ROR2/Wnt5a as biomarkers in stage 1 pure seminomas, WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells., WNT5A may play an important role in constructing an advantageous tumor microenvironment for the progression and development of human gastric cancer., Plasma Wnt5a levels are decreased in patient with type 2 diabetes mellitus., Our results suggest that Wnt5a is a major contributing factor to the increase in osteolytic bone lesions and hypercalcemia found in Adult T-cell leukemia/lymphoma patients, Wnt5a inhibits human monocyte-derived myeloid dendritic cell generation., Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3 -induced epithelial-mesenchymal transition. Thus, Smarcd3 epigenetically regulates epithelial-mesenchymal transition by activating WNT signaling pathways., Wnt5a signaling pathway may be involved in the malignancy of glioma., High WNT5A expression is associated with colon cancer., Wnt5a pathway may play a role in the pathogenesis of urothelial carcinoma of the bladder., DEX induces the upregulation of noncanonical Wnt ligand Wnt5a. Recombinant WNT5a protein induces CLAN formation through the noncanonical Wnt receptor ROR2/RhoA/ROCK signaling axis., Wnt5a assembles a Wnt-receptor-actin-myosin-polarity structure and directs polarized calcium gradients., It plays a important role in pathogenecity of frontotemporal lobar degeneration, which suggests a novel target for the therapeutic intervenion., Upregulation of Wnt5a promotes EMT and metastasis in pancreatic cancer models., MV and exosomes are critical for MPhi-induced invasion of cancer cells since they are responsible for upregulation of MPhi-Wnt 5a as well as for its delivery to the recipient cells via a reciprocal loop., our study provides evidence that the distinct activities of WNT5A in cancer can be attributed to the production of two WNT5A isoforms., findings support a new role for WNT5A in the metabolic reprogramming of cancer cells that is a context- dependent event, Wnt5a uses CD146 as a receptor to regulate cell migration., Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions., Wnt5a signals in hCMEC/D3 cells through activation of the Par/aPKC PCP complex, independently of the Wnt canonical beta-catenin-dependent pathway and significantly contributes to TJ integrity and endothelial apicobasal polarity., The expression levels of Wnt5a, p-JNK1 and p-paxillin in tumor tissues were correlated with each other., Ursolic acid suppressed the expression of Wnt5alpha/beta and beta-catenin, inducing apoptosis in prostate cancer cells., Wnt5a overproduction and SFRP5 deficiency in gastric mucosa may together play an important role in gastric inflammation and carcinogenesis., Our findings indicate that Wnt5a might act as tumor suppressor by inhibiting cell proliferation and attenuating EMT in colon cancer cells, WNT5A derived from bone stromal cells induced the expression of BMP-6 by CaP cells; BMP-6 in turn stimulated cellular proliferation of CaP cells., SFRP5 and WNT5A comprise a balanced duo that may regulate metabolic homeostasis in prepubertal children., differential Wnt11 immunoexpression in high-grade human serous ovarian cancer compared to low-grade human serous ovarian cancer could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels., The Wnt-5a was expressed and correlated with cell motility and infiltrative activity through the regulation of matrix metalloproteinase (MMP)-2 in glioma-derived cells., Results reveal pro-tumorigenic effects of WNT5A in nasopharyngeal carcinoma., Data show that the WNT/beta-CATENIN signaling cascade components, including WNT ligands WNT3 and WNT5A, is crucial for early odontogenesis., establish a directional crosstalk between calcium-sensing receptor and Wnt/beta-catenin signaling in keratinocyte differentiation via Wnt5a that acts as an autocrine stimulus in this process, Wnt5a may act as a tumor-suppressor gene in hepatocellular carcinoma, we demonstrate that innate immune functions of macrophages ensue at least partly through a homeostatic Wnt5a-Fz5-NF-kappaB (p65) circuit, which is Rac1 dependent., De novo WNT5A-associated autosomal dominant Robinow syndrome suggests specificity of genotype and phenotype., Our study suggests that wnt5a may play a role in the pathophysiology of psoriasis and its metabolic comorbidity such as insulin resistance., WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells., Data indicate that cell migration was inhibited in Wnt5a-inhibited melanoma cells., WIF-1 is frequently methylated and that Wnt5a acts as a tumor suppressor gene in colorectal carcinoma., Activation of noncanonical Wnt signaling through the up-regulation of WNT5A may promote a proinflammatory state in visceral adipose tissue contributing to the development of obesity-associated comorbidities., RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAF inhibitor challenge, and decreased the activity of prosurvival AKT signaling., data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-alpha., Results show that Wnt5a promoted epithelial-mesenchymal transition via PKCalpha in epithelial ovarian cancer., the findings suggested that miR-26a may function as a tumor suppressor in prostate cancer by targeting Wnt5a., The results demonstrate that Wnt5a induces monocyte chemotactic protein 1 production in gastric cancer, which is mediated by IL-1beta., The results demonstrated that overexpression of Wnt5a may play an important role in NSCLC angiogenesis and it may function via canonical Wnt signal pathway., Findings suggest that Wnt5a enhances cell migration through activation of Cdc42 and inactivation of RhoA in human corneal endothelial cells., Wnt-5a mRNA levels were significantly higher in hepatocellular carcinoma tissue than in the para-carcinoma tissue while Wnt-5a protein was absent or low, Aberrant methylation of APC gene was statistically significant associated with age over 50, DDK3 with male, SFRP4, WIF1, and WNT5a with increasing tumor stage SFRP4 and WIF1 with tumor differentiation and SFRP2 and SFRP5 with histological type, Wnt5a signaling increases IL-12 secretion by human dendritic cells and enhances IFN-gamma production by CD4+ T cells., This study thus provides evidence that the ability of WNT5A to promote cancer progression is dependent on the cellular context., WNT5A exhibits antitumor effects in prostate cancer cells and may be suitable as a prognostic marker and therapeutic target for prostate cancer and associated skeletal metastases, Wnt5a secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation., Wnt5a has a role in the pathogenesis of atherosclerosis and other inflammatory disorders [review], WNT5a acts as a proinflammatory factor in human ovarian granulosa cells. The up-regulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the phosphatidylinositol 3-kinase/AKT/NF-kappaB signaling pathway., WNT5A induced chemoresistance by regulation of G1-S transition in pancreatic cancer cells., Upregulation of Wnt5A was associated with metastasis and progression of cervical cancer., The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease., the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and beta-catenin-related genes in antagonizing the toxic effects of doxorubicin in cell lines and in clinical breast cancer samples., These data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance., In gastric cancer, HNF4alpha regulated WNT signalling through its target gene WNT5A., Serum wnt5a gene expression might be a potential biomarker for predicting the prognosis of acute on chronic hepatitis B liver failure., The Wnt5a/Ca 2+ /calcineurin/nuclear factor of the activated T signaling pathway in melanoma., Human placenta-derived Wnt-5a induces the expression of ICAM-1 and VCAM-1 in CD133(+)CD34(+)-hematopoietic progenitor cells., Wnt5a-Ror2 axis is constitutively activated in cancer cells and confers highly motile and invasive properties on cancer cells through the expression of matrix metalloproteinase genes and enhanced formation of invadopodia., Wnt5a activated Src family kinases (SFKs) and Wnt5a-dependent cancer cell proliferation was dependent on SFKs, yet blockade of receptor-mediated endocytosis did not affect cancer cell proliferation and SFK activity., These results suggest that Wnt5a expressed in PDL tissue plays specific roles in inducing collagen production by PDL cells through TGFbeta1-mediated upregulation of periostin expression., Heterozygous loss of WNT5A was correlated with shorter survival of breast cancer patients., Loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that activates the WNT/Ca(2+) pathway and MALAT1., Wnt5a is a potential suppressor of EMT; there is a novel Arf6/ERK signaling pathway for EGF-regulated Wnt5a expression at transcriptional level of gastric cancer cel, Data suggest that WNT5A is an important molecule in promoting stem cell characteristics in NPC, leading to tumorigenesis and metastasis., Osteogenic features of MSCs from ossification of yellow ligament patients are promoted by unmethylated WNT5A., results provide evidence that Wnt5a induces protein depalmitoylation, which promotes polarized protein localization and cell invasion., miR-217 functions as a tumor suppressor in osteosarcoma by suppressing Wnt5a expression., in hepatic stellate cells regulates inflammatory cytokine and collagen production and cell proliferation, independent of the canonical Wnt signaling pathway, Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/beta-catenin or Wnt5a/Ca(2+) pathways, The homozygous genotypes (CC for rs524153 and GG for rs504849) were associated with a lower WNT5A transcriptional level compared with the transcriptional level of those with wild-type genotypes., It is involved in tumor initiation, cancer stem cell maintenance and angiogenesis., Findings suggest that high receptor tyrosine kinase-like orphan receptor (ROR) 2 or proto-oncogene protein Wnt-5A (Wnt5a) expression is associated with poor prognosis in non-small cell lung cancer (NSCLC)., Data show that the WIF domain of Wnt Inhibitory Factor 1 (WIF1) is bound by C-terminal domains of Wnt proteins Wnt5a and Wnt7a at two sites., The results reveal higher WNT-5A protein levels and mRNA expression in a subgroup of gliomas compared to non-malignant control brain tissue. It also showes a significant correlation between WNT-5A in the tumor and presence of microglia/monocytes., WNT-5A is a crucial signaling molecule under investigation with efforts to not only delineate its signaling mechanisms and functions in physiological and pathological conditions, but also to develop strategies for its therapeutic targeting. [review], Forced overexpression of Wnt7B with or without TGFB1 treatment increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in Idiopathic Pulmonary Fibrosis myofibroblasts where Wnt5A was already highly expressed., WNT5A participates in the biology of odontogenic tumors and inflammatory cyst but not in developmental cyst., results corroborated previous findings of Ryk-mediated Wnt5a effect, and suggested a role for Ror2 in the Wnt5a machinery in glioblastoma, This study identifies an interaction between ROR1 and ROR2 that is required for Wnt5a signaling that promotes leukemia chemotaxis and proliferation., Wnt5a-Ror2 signaling enhances expression and secretion of CXCL16 in mesenchymal stem cells thereby activating CXCR6 expressed on tumor cells to promote proliferation., Mutation in WNT5A may serve as a susceptibility factor for Congenital Anomalies Of Kidney And Urinary Tract., Noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction., Epigenetic inactivation of the WNT5A promoter B involves both DNA methylation and histone modifications. Differential expression of the WNT5A alternative promoters A and B is a characteristic of osteosarcomas., Wnt5a is increased and beta-catenin is decreased in parenchyma from idiopathic pulmonary fibrosis patients.,
OMIM_DISEASE Robinow syndrome, autosomal dominant 1,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression. Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells. Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes., PTM:Glycosylation is necessary for secretion but not for activity., PTM:Palmitoylation is necessary for stimulation of cell migration, inhibition of the beta-catenin pathway and receptor binding., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN., tissue specificity:Expression is increased in differentiated thyroid carcinomas compared to normal thyroid tissue and anaplastic thyroid tumors where expression is low or undetectable. Expression is found in thyrocytes but not in stromal cells (at protein level).,
Wnt family member 5B(WNT5B) Wnt family member 5B(WNT5B) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12p13.3,
ENSEMBL_GENE_ID ENSG00000111186,
GENERIF_SUMMARY WNT5b is upregulated by beta-estradiol in tumor cell lines, WNT5B gene may contribute to conferring susceptibility to type 2 diabetes and may be involved in the pathogenesis of this disease through the regulation of adipocyte function., In leiomyoma cells, the regulation of Wnt5b expression by retinoids appears to be attenuated., Variation in WNT5B predisposes to type 2 diabetes in the absence of obesity., Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., This is significantly related to fat cell differentiation, suggesting its possible involvement in the onset of diabetes mellitus type 2 and metabolic syndrome., Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b, This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy., TGF-beta/Smad, integrin/integrin-linked kinase (ILK) and wnt/beta-catenin signaling pathways are involved in epithelial to mesenchymal transition in human renal fibrogenesis., These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA., WNT3 and WNT5B are critical factors, secreted from mesenchymal cancer cells, for instigating the epithelial cancer cell invasion., Ursolic acid suppressed the expression of Wnt5alpha/beta and beta-catenin, inducing apoptosis in prostate cancer cells., WNT5B is elevated in both in the tumor and the patients' serum from triple negative breast cancer., Knocking down Wnt5b expression reduced phospho-PKCA levels and cell migration., Report increased Wnt5b levels in adriamycin treated liver cancer stem cells within 4h of treatment., Results demonstrate that the Wnt5B pathway may play an important role in atypical teratoid rhabdoid tumor biology., The interaction between Wnt isoforms and their LRP6 cognate receptor depends on the jutting loop present in Wnt3a but absent in Wnt5b.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN.,
Wnt family member 6(WNT6) Wnt family member 6(WNT6) Related Genes Homo sapiens
CHROMOSOME 2,
CYTOBAND 2q35,
ENSEMBL_GENE_ID ENSG00000115596,
GENERIF_SUMMARY Wnt6 plays an important role in tooth development by promoting human dental papilla cell differentiation, without significant effects on cell proliferation., The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma., WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to anthracycline drugs, WNT6 activates the JNK signaling pathway in HDPCs, leading to migration and differentiation., analysis of missense mutation in WNT6 in couples with unexplained recurrent miscarriage,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN.,
Wnt family member 7A(WNT7A) Wnt family member 7A(WNT7A) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p25,
ENSEMBL_GENE_ID ENSG00000154764,
GENERIF_SUMMARY WNT7a gene expression is regulated by TGF-beta1 through the intracellular beta-catenin-TCF pathway, provides support that E-cadherin induction by WNT/beta-catenin signaling is an evolutionarily conserved pathway operative in lung cancer cells and that loss of expression may be important in lung cancer development or progression, WNT7A mutations are an unlikely cause of Mullerian duct derivative abnormalities in humans, Wnt-7a is associated with cartilage destruction by regulating the maintenance of differentiation status and the apoptosis of articular chondrocytes via different mechanisms, analysis of multiple Wnt mRNAs in non-small cell lung cancer (NSCLC) cell lines and primary lung tumors revealed markedly decreased Wnt-7a expression compared with normal short-term bronchial epithelial cell lines and normal uninvolved lung tissue, By regulating the proliferation of corneal epithelial cells, Wnt-7a and MMP-12 appear to contribute to corneal wound healing, Partial loss of WNT7A causes Fuhrmann syndrome, whereas the more severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations., ERK5-dependent activation of PPARgamma represents a major effector pathway mediating the anti-tumorigenic effects of Wnt 7a and Fzd 9 in non-small cell lung cancer cells, the absence of tumour-specific somatic events in WNT7A and HDAC11 suggests that these genes are unlikely to have a classical tumour suppressor gene role in sporadic malignant pancreatic endocrine tumours, WNT7A plays a role in the pathophysiology of endometriosis., These biological tools could help lead to a better understanding of Wnt-Fzd interactions and the identification of new modulators of Wnt signaling., WNT7A gene is unlikely to be a major contributor to the aetiology of familial congenital talipes equinovarus, Based on these results it is unlikely CAND2 and WNT7a are the major genes that causes clubfoot., Mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome., Female mammals with a deficiency in the product of Wnt7a gene are infertile as a result of abnormal development of the uterus and the oviducts., Results suggest that this diminished expression of the WNT7A gene may be related to a supposed protection of fragile X syndrome patients to develop cancer., The activity of the Sprouty4 promoter is increased by Wnt7A/Frizzled 9 homolog (Fzd9) signaling through peroxisome proliferator-activated receptor gamma in lung cancer cells., Expression levels of Wnt7A, beta-catenin, and FoxA1, along with cell-type specific markers, are observed to vary with differentiation and often also in response to the presence of heparin during the time of exposure to heparin., Abnormalities in the Wnt7a pathway (located in the dorsal ectoderm) produce several clinically relevant conditions., High Wnt7a expression in ovarian cancer may be associated with poor prognosis., A novel homozygous missense mutation in coding exon 4 of the WNT7A was detected in both affected daughters (c.664C > T) leading to an amino acid exchange from arginine to tryptophan (p.Arg222Trp; R222W)., Partial loss of WNT7A function resulted in Fuhrmann syndrome, while complete loss of WNT7A function resulted in the more severe phenotype of Al-Awadi-Raas-Rothschild syndrome., The novel missense homozygous mutation (p.Gly204Ser) in the WNT7A gene is a unique mutation in the degree of loss of function in the upper limb development which ranges from mild to complete absence of both upper limbs (amelia)., Mutations in the coding sequence of WNT7A are not responsible for mullerian duct abnormalities in the Chinese population., reexpression of WNT7A during malignant transformation of ovarian epithelial cells plays a critical role in ovarian cancer progression mediated by WNT/beta-catenin signaling pathway., Wnt7a has a role in postmenstrual regeneration and proliferation of endometrial glands and luminal epithelium in primates, Wnt7a is lost by methylation in a subset of tumors and that this methylation is maintained by DNMT1, Gene expression profiling identifies WNT7A as a key SVZ-glial factor lacking in OB-glia that enhances self-renewal, thereby improving the propagation of OB-NSC cultures., WNT7A gene is inactivated by genetic/epigenetic alterations in clear cell RCC and demonstrates tumor suppressor properties, Overexpression of Wnt7a may contribute to the progression of endometrial cancer and thus may serve as a new biomarker to predict the prognosis of endometrial cancer., Novel mutations in the WNT7A gene in two unrelated cases of Al-Awadi Raas-Rothschild syndrome., Binding of Wnt7a to Fzd7 leads to an activation of noncanonical Wnt signaling, resulting in directed myogenic stem cell migration and enhanced engraftment., findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases, Prognosis was significantly more favorable for patients with high Wnt7A expression., loss of the Wnt7a gene induced by promoter methylation might be a prognostic factor for non-small cell lung carcinoma, Wnt7a has a role in specifying the fate of neural crest-like cells via suppression of notch in the human skin microenvironment, identified Iloprost, a prostacyclin analog, which initiates downstream signaling cascades similar to that of Wnt7a, as a novel inducer of cellular senescence, presenting potential future clinical translational strategies, this is the first study reporting reduced WNT7A levels in cervical cancer -derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration., Wnt7a overexpression is associated with an unfavorable prognosis and that positive Wnt7a may be an independent prognosis factor influencing OS and DFS prediction in colorectal cancer patients., Wnt7a is involved in the transformation of the retinal pigment epithelium.,
OMIM_DISEASE Fuhrmann syndrome, Ulna and fibula, absence of, with severe limb deficiency,
SP_COMMENT disease:Defects in WNT7A are a cause of Fuhrmann syndrome [MIM:228930]; also called fibular aplasia or hypoplasia femoral bowing and poly- syn- and oligodactyly. Fuhrmann syndrome is a distinct limb-malformation disorder characterized also by various degrees of limb aplasia/hypoplasia and joint dysplasia., disease:Defects in WNT7A are the cause of limb/pelvis-hypoplasia/aplasia syndrome (LPHAS) [MIM:276820]; also called absence of ulna and fibula with severe limb deficiency. LPHAS is a limb-malformation disorder characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Signaling by Wnt-7a allows sexually dimorphic development of the mullerian ducts., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN., tissue specificity:Expression is restricted to placenta, kidney, testis, uterus, fetal lung, and fetal and adult brain.,
Wnt family member 7B(WNT7B) Wnt family member 7B(WNT7B) Related Genes Homo sapiens
CHROMOSOME 22,
CYTOBAND 22q13,
ENSEMBL_GENE_ID ENSG00000188064,
GENERIF_SUMMARY These data demonstrate that mesenchymal stem cells from mice and humans produce Wnt proteins and TGF-beta1 that respectively stimulate lung fibroblast proliferation and matrix production., Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., Wnt7B was expressed at high concentrations in regions of active hyperplasia, metaplasia, and fibrotic change in idiopathic pulmonary fibrosis patients., Pdgf signaling potentiates Wnt2-Wnt7b signaling to promote high levels of Wnt activity in mesenchymal progenitors that is required for proper development of endoderm-derived organs, such as the lung, Results suggest that AR-regulated WNT7B signaling is critical for the growth of CRPC and development of the osteoblastic bone response characteristic of advanced prostate cancer., WNT7B can serve as a primary determinant of differential Wnt/beta-catenin activation in pancreatic adenocarcinoma., Results illustrated the critical role of myeloid WNT7B in tumor progression, acting at the levels of angiogenesis, invasion, and metastasis., WNT7B as a novel susceptibility gene for axial length and corneal curvature and is associated with myopia and extreme myopia., Forced overexpression of Wnt7B with or without TGFB1 treatment increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in Idiopathic Pulmonary Fibrosis myofibroblasts where Wnt5A was already highly expressed., the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., subunit:Interacts with PORCN., tissue specificity:Moderately expressed in fetal brain, weakly expressed in fetal lung and kidney, and faintly expressed in adult brain, lung and prostate.,
Wnt family member 8A(WNT8A) Wnt family member 8A(WNT8A) Related Genes Homo sapiens
CHROMOSOME 5,
CYTOBAND 5q31,
ENSEMBL_GENE_ID ENSG00000061492,
GENERIF_SUMMARY Expression and regulation of WNT8A mRNA in human tumor cell lines, the WNT8A gene is involved in the susceptibility to HSCR, and plays an important role in the occurrence and development of Hirschsprung's disease.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus., similarity:Belongs to the Wnt family.,
Wnt family member 8B(WNT8B) Wnt family member 8B(WNT8B) Related Genes Homo sapiens
CHROMOSOME 10,
CYTOBAND 10q24,
ENSEMBL_GENE_ID ENSG00000075290,
GENERIF_SUMMARY significantly up-regulated in gastric cancer cell lines KATO-III (signet-ring cell carcinoma) and MKN45 (poorly differentiated adenocarcinoma), and also in 5 out of 10 cases of primary gastric cancer, Expression and regulation of WNT8B mRNA in human tumor cell lines, WNT8B expression in hepatocyte progenitors derived from human ES cells is due to POU5F1 (OCT3/OCT4) and GATA3, and WNT8B expression in diffuse-type gastric cancer is due to POU5F1 and GATA6, WNT8b and SHH mutations and abnormal expressions are present in the peripheral blood of children with sporadic Hirschsprung disease.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus., similarity:Belongs to the Wnt family., tissue specificity:Expression is restricted to the brain, and more specifically to the forebrain.,
Wnt family member 9A(WNT9A) Wnt family member 9A(WNT9A) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1q42,
ENSEMBL_GENE_ID ENSG00000143816,
GENERIF_SUMMARY Found clustered with WNT3A on 1q42. ., 5'-flanking promoter region was significantly divergent between human WNT9A and rodent Wnt9a genes., These results suggests the expression level of human Wnt9a in MCF-7 that breast cancer may play a role in adjusting the rate of cellular proliferation., cDNA gene expression array of Wnt signaling pathway target genes demonstrated significant changes, including 4.5-fold induction of Wnt 9A and suppression of Dickkopf 3 and RHOU genes., Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects., Using DirectDNA sequencing analysis, we detected ATBF1, CYLD, PARK2 and WNT9A mutations in stomach and colorectal cancers, Transgenic wnt9a is required for palatal extension wherein the chondrocytes form a proliferative front, undergo morphological change and intercalate to form the ethmoid plate., These studies reveal how carrageenan exposure can lead to transcriptional events in colonic epithelial cells through decline in arylsulfatase B activity, with subsequent impact on C4S, galectin-3, Sp1, and Wnt9A, Silencing Wnt9A increased the expression of CHST11 in the colonic epithelial cells, and chromatin immunoprecipitation assay demonstrated enhancing effects of Wnt9A siRNA and exogenous BMP4 on the CHST11 promoter, expression is enhanced in idiopathic carpal tunnel syndrome,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family.,
Wnt family member 9B(WNT9B) Wnt family member 9B(WNT9B) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17q21,
ENSEMBL_GENE_ID ENSG00000158955,
GENERIF_SUMMARY Mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome., secretion of WNT2B and WNT9B and stabilization of beta-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism, The signals from the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the progenitor cells., Two novel mutations (a missense mutation in exon 1, and one in the 3-UTR) may be pathogenic variants in Mayer-Rokitansky-Kuster-Hauser syndrome patients and warrant further functional study., results indicate that mutations in the coding sequence of WNT9B are not responsible for Mullerian duct abnormalities in the Chinese population, Genome association study shows a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B in patients with classic bladder exstrophy., This association study successfully identified two susceptibility Single Nucleotide Polymorphisms, (WNT9B and PBX1) associated with Mayer-Rokitansky-Kuster-Hauser syndrome risk, both separately and interactively.,
SP_COMMENT function:Ligand for members of the frizzled family of seven transmembrane receptors., function:Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters., similarity:Belongs to the Wnt family., tissue specificity:Moderately expressed in fetal kidney and adult kidney. Also found in brain.,