Genomes and Genes
Gene Symbol: Tcf7l2
Description: transcription factor 7 like 2
Alias: transcription factor 7-like 2, transcription factor 7-like 2 (T-cell specific, HMG-box)
- Yi F, Brubaker P, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005;280:1457-64 pubmed..We have therefore identified a unique mechanism that regulates glu expression in gut endocrine cells only. Tissue-specific expression of TCF factors thus may play a role in the diversity of the Wnt pathway. ..
- Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters P, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19:379-83 pubmed..The constitutive activity of Tcf-4 in APC-deficient human epithelial cells may contribute to their malignant transformation by maintaining stem-cell characteristics. ..
- Hong C, Chou Y, Lin Y, Wu C. MAD2B, a novel TCF4-binding protein, modulates TCF4-mediated epithelial-mesenchymal transdifferentiation. J Biol Chem. 2009;284:19613-22 pubmed publisher..Thus, MAD2B is a novel TCF4-interacting protein. This study provides the first evidence for the involvement of MAD2B in TCF4-mediated epithelial-mesenchymal transdifferentiation. ..
- van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241-50 pubmed..Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells. ..
- Norton L, Fourcaudot M, Abdul Ghani M, Winnier D, Mehta F, Jenkinson C, et al. Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism. Diabetologia. 2011;54:3132-42 pubmed publisherThe mechanisms by which transcription factor 7-like 2 (TCF7L2) regulates the pathways that are important in the pathogenesis of type 2 diabetes are unknown...
- Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, et al. Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse. Mol Cell Biol. 1998;18:1248-56 pubmed..These data demonstrate a direct link between Wnt stimulation and beta-catenin/Tcf transcriptional activation and imply a role for mTcf-3 and -4 in early Wnt-driven developmental decisions in the mouse embryo. ..
- Shulewitz M, Soloviev I, Wu T, Koeppen H, Polakis P, Sakanaka C. Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer. Oncogene. 2006;25:4361-9 pubmed..Our results indicate that both Sfrp1 and TCF-4 repress Wnt signaling in breast tissue and their downregulation contributes to the activation of Wnt signaling. ..
- Weise A, Bruser K, Elfert S, Wallmen B, Wittel Y, Wöhrle S, et al. Alternative splicing of Tcf7l2 transcripts generates protein variants with differential promoter-binding and transcriptional activation properties at Wnt/beta-catenin targets. Nucleic Acids Res. 2010;38:1964-81 pubmed publisher..The mouse Tcf7l2 gene is subject to alternative splicing...
- Kennell J, O Leary E, Gummow B, Hammer G, MacDougald O. T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol Cell Biol. 2003;23:5366-75 pubmed..Thus, we propose that TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha. ..
- Korinek V, Barker N, Morin P, van Wichen D, de Weger R, Kinzler K, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997;275:1784-7 pubmed..Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. ..
- Cho E, Dressler G. TCF-4 binds beta-catenin and is expressed in distinct regions of the embryonic brain and limbs. Mech Dev. 1998;77:9-18 pubmed..5 and is limited to mesenchymal cells surrounding the areas of chondrification. These data indicate a function for Tcf-4 in neural and limb development, two tissues where Wnt signaling plays an essential role. ..
- Drake I, Wallström P, Hindy G, Ericson U, Gullberg B, Bjartell A, et al. TCF7L2 type 2 diabetes risk variant, lifestyle factors, and incidence of prostate cancer. Prostate. 2014;74:1161-70 pubmed publisherVariation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors...
- Quasnichka H, Slater S, Beeching C, Boehm M, Sala Newby G, George S. Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression. Circ Res. 2006;99:1329-37 pubmed..We therefore suggest that the N-cadherin and beta-catenin/TCF signaling pathway is a key modulator of VSMC proliferation via regulation of these 2 beta-catenin/TCF responsive genes. ..
- Wu L, Hsieh C, Pei D, Hung Y, Kuo S, Lin E. Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol Dial Transplant. 2009;24:3360-6 pubmed publisher..receptor (GHSR), peroxisome proliferator-activated receptor gamma (PPARgamma) and transcription factor 7-like 2 (TCF7L2). There were 216 T2D patients diagnosed with DN and 178 age-similar T2D without DN (control) subjects...
- Lambertini E, Franceschetti T, Torreggiani E, Penolazzi L, Pastore A, Pelucchi S, et al. SLUG: a new target of lymphoid enhancer factor-1 in human osteoblasts. BMC Mol Biol. 2010;11:13 pubmed publisher..These findings will help to further understand the regulation of the human SLUG gene and reveal the biological functions of SLUG in the context of bone tissue. ..
- Shu L, Matveyenko A, Kerr Conte J, Cho J, McIntosh C, Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet. 2009;18:2388-99 pubmed publisherRecent human genetics studies have revealed that common variants of the TCF7L2 (T-cell factor 7-like 2, formerly known as TCF4) gene are strongly associated with type 2 diabetes mellitus (T2DM)...
- Blackman S, Hsu S, Ritter S, Naughton K, Wright F, Drumm M, et al. A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis. Diabetologia. 2009;52:1858-65 pubmed publisher..A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 ..
- Jones S, Zhang X, Parsons D, Lin J, Leary R, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801-6 pubmed publisher..Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis...
- Brugmann S, Goodnough L, Gregorieff A, Leucht P, ten Berge D, Fuerer C, et al. Wnt signaling mediates regional specification in the vertebrate face. Development. 2007;134:3283-95 pubmed..Collectively, these data elucidate a new role for Wnt signaling in regional specification of the vertebrate face, and suggest possible mechanisms whereby species-specific facial features are generated. ..
- Brinkmeier M, Potok M, Davis S, Camper S. TCF4 deficiency expands ventral diencephalon signaling and increases induction of pituitary progenitors. Dev Biol. 2007;311:396-407 pubmed..of several members of this family during pituitary development and the functional role of one member, TCF4 (TCF7L2), in the induction of the pituitary primordium...
- Ghiselli G, Agrawal A. The human D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway. Biochem J. 2005;390:493-9 pubmed..The data obtained are consistent with the idea that the beta-catenin-TCF4 transactivation pathway plays a major role in modulating GLCE expression, thus contributing to the regulation of HS biosynthesis and its structural organization. ..
- Da Silva Xavier G, Loder M, McDonald A, Tarasov A, Carzaniga R, Kronenberger K, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 2009;58:894-905 pubmed publisherPolymorphisms in the human TCF7L2 gene are associated with reduced insulin secretion and an increased risk of type 2 diabetes. However, the mechanisms by which TCF7L2 affect insulin secretion are still unclear...
- Kanamori M, Sandy P, Marzinotto S, Benetti R, Kai C, Hayashizaki Y, et al. The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells. J Biol Chem. 2003;278:38758-64 pubmed..These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway. ..
- Nateri A, Spencer Dene B, Behrens A. Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature. 2005;437:281-5 pubmed..Therefore, the phosphorylation-dependent interaction between c-Jun and TCF4 regulates intestinal tumorigenesis by integrating JNK and APC/beta-catenin, two distinct pathways activated by WNT signalling. ..
- Ye F, Chen Y, Hoang T, Montgomery R, Zhao X, Bu H, et al. HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci. 2009;12:829-38 pubmed publisher..We further identified the oligodendrocyte-restricted transcription factor TCF7L2/TCF4 as a bipartite co-effector of beta-catenin for regulating oligodendrocyte differentiation...
- Miller K, Barrow J, Collinson J, Davidson S, Lear M, Hill R, et al. A highly conserved Wnt-dependent TCF4 binding site within the proximal enhancer of the anti-myogenic Msx1 gene supports expression within Pax3-expressing limb bud muscle precursor cells. Dev Biol. 2007;311:665-78 pubmed..The results of these studies provide evidence of a mechanistic link between the Wnt/TCF and the Msx1/Pax3/MyoD pathways within limb bud muscle precursor cells. ..
- Ling C, Wang L, Wang Z, Xu L, Sun L, Yang H, et al. A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas. PLoS ONE. 2015;10:e0116753 pubmed publisher..We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases...
- Chen C, Huang C, Huang S, Lin V, Yu C, Chang T, et al. Genetic interaction analysis of TCF7L2 for biochemical recurrence after radical prostatectomy in localized prostate cancer. Int J Med Sci. 2015;12:243-7 pubmed publisher..We hypothesize that genetic variants in the Wnt pathway effector, Transcription factor 7-like 2 (TCF7L2), may influence clinical outcomes in prostate cancer...
- Yook J, Li X, Ota I, Hu C, Kim H, Kim N, et al. A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006;8:1398-406 pubmed..As dysregulated Wnt signalling marks a diverse array of cancerous tissue types, the identification of a beta-catenin-TCF-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated EMT programmes. ..
- Fre S, Pallavi S, Huyghe M, Lae M, Janssen K, Robine S, et al. Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci U S A. 2009;106:6309-14 pubmed publisher..Importantly, our experimental evidence raises the possibility that Notch activation might be an essential initial event triggering colorectal cancer...
- Amir A, Barua M, McKnight N, Cheng S, Yuan X, Balk S. A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem. 2003;278:30828-34 pubmed
- Figeac F, Uzan B, Faro M, Chelali N, Portha B, Movassat J. Neonatal growth and regeneration of beta-cells are regulated by the Wnt/beta-catenin signaling in normal and diabetic rats. Am J Physiol Endocrinol Metab. 2010;298:E245-56 pubmed publisher..To this aim, TCF7L2, the distal effector of the canonical Wnt pathway, was knocked down in groups of normal and diabetic rats by the ..
- Lauenborg J, Grarup N, Damm P, Borch Johnsen K, Jørgensen T, Pedersen O, et al. Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab. 2009;94:145-50 pubmed publisher..Type 2 diabetes risk variants in TCF7L2, CDKAL1, SLC30A8, HHEX/IDE, CDKN2A/2B, IGF2BP2, FTO, TCF2, PPARG, KCNJ11, and WFS1 loci were genotyped in a cohort ..
- Oh K, Park J, Kim S, Oh H, Choi C, Koo S. TCF7L2 modulates glucose homeostasis by regulating CREB- and FoxO1-dependent transcriptional pathway in the liver. PLoS Genet. 2012;8:e1002986 pubmed publisherPeripheral insulin resistance contributes to the development of type 2 diabetes. TCF7L2 has been tightly associated with this disease, although the exact mechanism was largely elusive...
- Wielenga V, Smits R, Korinek V, Smit L, Kielman M, Fodde R, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol. 1999;154:515-23 pubmed..Our results indicate that CD44 expression is part of a genetic program controlled by the beta-catenin/Tcf-4 signaling pathway and suggest a role for CD44 in the generation and turnover of epithelial cells. ..
- Kanda S, Miyata Y, Kanetake H. T-cell factor-4-dependent up-regulation of fibronectin is involved in fibroblast growth factor-2-induced tube formation by endothelial cells. J Cell Biochem. 2005;94:835-47 pubmed..Taken together, interaction of alpha(5)beta(1) integrin and fibronectin is involved in FGF-2-induced tube formation by endothelial cells and up-regulation of fibronectin through TCF-4 seemed to be involved in this process. ..
- Mathew S, Hansen J, Merrell A, Murphy M, Lawson J, Hutcheson D, et al. Connective tissue fibroblasts and Tcf4 regulate myogenesis. Development. 2011;138:371-84 pubmed publisher..Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4(GFPCre) mice allow genetic manipulation of ..
- Liu P, Chang Y, Jiang Y, Chen W, Chang T, Kuo S, et al. Genetic variants of TCF7L2 are associated with insulin resistance and related metabolic phenotypes in Taiwanese adolescents and Caucasian young adults. J Clin Endocrinol Metab. 2009;94:3575-82 pubmed publisherThe effect of TCF7L2 rs7903146 on glucose homeostasis is considered primarily due to impaired insulin secretion in European populations...
- Yamada M, Ohnishi J, Ohkawara B, Iemura S, Satoh K, Hyodo Miura J, et al. NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF). J Biol Chem. 2006;281:20749-60 pubmed..Collectively, our findings raise the possibility that NARF functions as a novel ubiquitin-ligase to suppress the Wnt-beta-catenin signaling. ..
- Friedman M, Oyserman S, Hankenson K. Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2. J Biol Chem. 2009;284:14117-25 pubmed publisher..These studies show that Wnt11 signals through beta-catenin, activating Rspo2 expression, which is then required for Wnt11-mediated osteoblast maturation. ..
- Ross S, Hemati N, Longo K, Bennett C, Lucas P, Erickson R, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950-3 pubmed..Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination. ..
- Luo Y, Wang H, Han X, Ren Q, Wang F, Zhang X, et al. Meta-analysis of the association between SNPs in TCF7L2 and type 2 diabetes in East Asian population. Diabetes Res Clin Pract. 2009;85:139-46 pubmed publisherTo evaluate the effect of TCF7L2 on genetic susceptibility of type 2 diabetes (T2DM) in East Asian population by using the meta-analysis...
- Roose J, Clevers H. TCF transcription factors: molecular switches in carcinogenesis. Biochim Biophys Acta. 1999;1424:M23-37 pubmed..We will discuss Tcf signaling upon interaction with different partners, resulting in activator and repressor roles of Tcf factors in the light of carcinogenic events. ..
- Ogawa S, Goto W, Orimo A, Hosoi T, Ouchi Y, Muramatsu M, et al. Molecular cloning of a novel RING finger-B box-coiled coil (RBCC) protein, terf, expressed in the testis. Biochem Biophys Res Commun. 1998;251:515-9 pubmed..Structural similarity raises the possibilities that the terf gene might be also involved in carcinogenesis or cell transformation. ..
- Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787-90 pubmed..These results indicate that regulation of beta-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta-catenin. ..
- Nguyen H, Merrill B, Polak L, Nikolova M, Rendl M, Shaver T, et al. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet. 2009;41:1068-75 pubmed publisher..We established roles for Tcf3 and Tcf4 in long-term maintenance and wound repair of both epidermis and hair follicles, suggesting that Tcf proteins have both Wnt-dependent and Wnt-independent roles in lineage determination. ..
- Kim M, Kim S, Ahn C, Yoo N, Lee S. Frameshift mutations of Wnt pathway genes AXIN2 and TCF7L2 in gastric carcinomas with high microsatellite instability. Hum Pathol. 2009;40:58-64 pubmed publisher..Both AXIN2 and TCF7L2 genes in the Wnt pathway possess mononucleotide repeats in their coding sequences and are considered as candidate ..
- van Es J, Jay P, Gregorieff A, van Gijn M, Jonkheer S, Hatzis P, et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol. 2005;7:381-6 pubmed..These observations imply that Wnt signals in the crypt can separately drive a stem-cell/progenitor gene programme and a Paneth-cell maturation programme. In intestinal cancer, both gene programmes are activated simultaneously...
- He T, Sparks A, Rago C, Hermeking H, Zawel L, da Costa L, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509-12 pubmed..These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers. ..
- McCarthy T, Centrella M. Novel links among Wnt and TGF-beta signaling and Runx2. Mol Endocrinol. 2010;24:587-97 pubmed publisher..Therefore, we propose that cross talk between the Wnt and TGF-beta pathways, which converge on Runx2, both promotes and attenuates individual aspects of osteoblast maturation. ..
- Maeda O, Usami N, Kondo M, Takahashi M, Goto H, Shimokata K, et al. Plakoglobin (gamma-catenin) has TCF/LEF family-dependent transcriptional activity in beta-catenin-deficient cell line. Oncogene. 2004;23:964-72 pubmed
- Gregorieff A, Grosschedl R, Clevers H. Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos. EMBO J. 2004;23:1825-33 pubmed..Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members. ..
- Daniels D, Weis W. ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors and the general coactivator p300 using independent structural modules. Mol Cell. 2002;10:573-84 pubmed..The C-terminal armadillo repeats of beta-catenin may be an attractive target for compounds designed to disrupt aberrant beta-catenin-mediated transcription associated with various cancers. ..
- Liu Z, Habener J. Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem. 2008;283:8723-35 pubmed publisher..Inhibition of Wnt signaling by small interfering RNAs to beta-catenin or a dominant-negative TCF7L2 decreases both basal and Exd4-induced beta cell proliferation...
- Zhou Y, Zhang E, Berggreen C, Jing X, Osmark P, Lang S, et al. Survival of pancreatic beta cells is partly controlled by a TCF7L2-p53-p53INP1-dependent pathway. Hum Mol Genet. 2012;21:196-207 pubmed publisherThe transcription factor T-cell factor 7-like 2 (TCF7L2) confers type 2 diabetes risk mainly through impaired insulin secretion, perturbed incretin effect and reduced beta-cell survival...