Genomes and Genes
Gene Symbol: LEF1
Description: lymphoid enhancer binding factor 1
Alias: LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer-binding factor 1, T cell-specific transcription factor 1-alpha, TCF1-alpha
- Brantjes H, Roose J, van de Wetering M, Clevers H. All Tcf HMG box transcription factors interact with Groucho-related co-repressors. Nucleic Acids Res. 2001;29:1410-9 pubmed..Although Grg-5 contains the GP homology domain that mediates HDAC binding in long Grg proteins, Grg-5 fails to bind this co-repressor, explaining how it can de-repress transcription. ..
- Metzeler K, Heilmeier B, Edmaier K, Rawat V, Dufour A, Dohner K, et al. High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia. Blood. 2012;120:2118-26 pubmed publisherLymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor of Wnt signaling...
- Travis A, Amsterdam A, Belanger C, Grosschedl R. LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. Genes Dev. 1991;5:880-94 pubmed..Moreover, forced expression of recombinant LEF-1 in late stage B cells increases TCR alpha enhancer function. Taken together, these data suggest that LEF-1 is a regulatory participant in lymphocyte gene expression and differentiation. ..
- Nguyen A, Rosner A, Milovanovic T, Hope C, Planutis K, Saha B, et al. Wnt pathway component LEF1 mediates tumor cell invasion and is expressed in human and murine breast cancers lacking ErbB2 (her-2/neu) overexpression. Int J Oncol. 2005;27:949-56 pubmedThis study examines the role of LEF1, a component of the Wnt signaling pathway, in human breast and murine mammary carcinoma and its relationship to ErbB2 (her-2/neu) expression...
- Gutierrez A, Tschumper R, Wu X, Shanafelt T, Eckel Passow J, Huddleston P, et al. LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood. 2010;116:2975-83 pubmed publisher..aberrant expression of the Wnt pathway transcription factor and target gene lymphoid enhancer binding factor-1 (LEF1) in chronic lymphocytic leukemia (CLL)...
- van de Wetering M, Oosterwegel M, Dooijes D, Clevers H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 1991;10:123-32 pubmed..These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype. ..
- Jesse S, Koenig A, Ellenrieder V, Menke A. Lef-1 isoforms regulate different target genes and reduce cellular adhesion. Int J Cancer. 2010;126:1109-20 pubmed publisher..Our findings indicate that expression of alternatively spliced Lef-1 isoforms is involved in the determination of proliferative or migratory characteristics of pancreatic carcinoma cells. ..
- Wang W, Ji P, Steffen B, Metzger R, Schneider P, Halfter H, et al. Alterations of lymphoid enhancer factor-1 isoform expression in solid tumors and acute leukemias. Acta Biochim Biophys Sin (Shanghai). 2005;37:173-80 pubmed..Taken together, these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia. ..
- Skokowa J, Welte K. LEF-1 is a decisive transcription factor in neutrophil granulopoiesis. Ann N Y Acad Sci. 2007;1106:143-51 pubmed..In summary we demonstrated that LEF-1 is not only crucial in lymphopoiesis, but also in myelopoiesis, documenting new functions of LEF-1. ..
- Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S. Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling. EMBO J. 2002;21:2703-14 pubmed..This study therefore suggests that the MITF/TFE3 family is a new class of nuclear modulators for LEF-1, which may ensure efficient propagation of Wnt signals in many types of cells. ..
- Prieve M, Guttridge K, Munguia J, Waterman M. Differential importin-alpha recognition and nuclear transport by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer factor 1 and T-cell factor 1. Mol Cell Biol. 1998;18:4819-32 pubmed..GFP-LEF-1 readily localizes to the nucleus, whereas GFP-TCF-1 remains in the cytoplasm. Thus, LEF-1 and TCF-1 differ in several aspects of nuclear localization. ..
- Bucan V, Mandel K, Bertram C, Lazaridis A, Reimers K, Park Simon T, et al. LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells. Genes Cells. 2012;17:559-67 pubmed publisher..Taken together, our results indicate a pivotal role of LEF-1 in the regulation of proliferation and MMP-7 transcription in breast cancer cells. ..
- Ishitani T, Ninomiya Tsuji J, Matsumoto K. Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling. Mol Cell Biol. 2003;23:1379-89 pubmed..These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity. ..
- Behrens J, von Kries J, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, et al. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996;382:638-42 pubmed..Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus. ..
- Lin A, Chua M, Choi Y, Yeh W, Kim Y, Azzi R, et al. Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker. PLoS ONE. 2011;6:e16636 pubmed publisher..we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with ..
- Brannon M, Gomperts M, Sumoy L, Moon R, Kimelman D. A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev. 1997;11:2359-70 pubmed
- Nguyen D, Chiang A, Zhang X, Kim J, Kris M, Ladanyi M, et al. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell. 2009;138:51-62 pubmed publisher..The WNT/TCF target genes HOXB9 and LEF1 are identified as mediators of chemotactic invasion and colony outgrowth...
- ARCE L, Pate K, Waterman M. Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression. BMC Cancer. 2009;9:159 pubmed publisher..The variable ability of Groucho/TLE to oppose Wnt signaling in colon cancer cells suggests there may be defects in one or more of these steps. ..
- Skokowa J, Cario G, Uenalan M, Schambach A, Germeshausen M, Battmer K, et al. LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. Nat Med. 2006;12:1191-7 pubmed..These observations indicate that LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with CN. ..
- 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. ..
- Levanon D, Goldstein R, Bernstein Y, Tang H, Goldenberg D, Stifani S, et al. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Proc Natl Acad Sci U S A. 1998;95:11590-5 pubmed..These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling. ..
- Li Y, Wang L, Zhang M, Melamed J, Liu X, Reiter R, et al. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth, and invasion. Cancer Res. 2009;69:3332-8 pubmed publisher..In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate ..
- Li T, Ting J, Yokoyama N, Bernstein A, van de Wetering M, Waterman M. Wnt activation and alternative promoter repression of LEF1 in colon cancer. Mol Cell Biol. 2006;26:5284-99 pubmedAlternative promoters within the LEF1 locus produce polypeptides of opposing biological activities. Promoter 1 produces full-length LEF-1 protein, which recruits beta-catenin to Wnt target genes...
- Prieve M, Guttridge K, Munguia J, Waterman M. The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins. J Biol Chem. 1996;271:7654-8 pubmed..We find a surprising and significant difference in the expression pattern of pendulin and mSrp1 mRNA, suggesting that these two Srp1 proteins are distinguishable in function as well as sequence. ..
- Jimenez J, Jang G, Semler B, Waterman M. An internal ribosome entry site mediates translation of lymphoid enhancer factor-1. RNA. 2005;11:1385-99 pubmedThe lymphoid enhancer factor-1 LEF1 locus produces multiple mRNAs via alternative promoters. Full-length LEF-1 protein is produced via translation of an mRNA with a 1...
- Hecht A, Stemmler M. Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4. J Biol Chem. 2003;278:3776-85 pubmed..We found that TCF4E but not LEF1 supported beta-catenin-dependent activation of the Cdx1 promoter, whereas LEF1 specifically activated the Siamois ..
- Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 2001;15:3088-103 pubmedThe Wnt-responsive transcription factor LEF1 can activate transcription in association with beta-catenin and repress transcription in association with Groucho...
- Sierra J, Yoshida T, Joazeiro C, Jones K. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 2006;20:586-600 pubmed..We conclude that, in addition to regulating the stability of beta-cat, APC facilitates CtBP-mediated repression of Wnt target genes in normal, but not in colorectal cancer cells. ..
- Mao C, Byers S. Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials. Crit Rev Eukaryot Gene Expr. 2011;21:207-36 pubmed..switch is also achieved by the cell-context-dependent expression of four members (TCF7, TCF7L1, TCF7L2, and LEF1) and numerous variants, which display differential DNA binding affinity and specificity, repression strength, ..
- Ross D, Kadesch T. The notch intracellular domain can function as a coactivator for LEF-1. Mol Cell Biol. 2001;21:7537-44 pubmed..Our data therefore describe a new nuclear target of Notch signaling and a new coactivator for LEF-1. ..
- Wang S, Nan K, Wang Y, Wang W, Tian T. The balance between two isoforms of LEF-1 regulates colon carcinoma growth. BMC Gastroenterol. 2012;12:53 pubmed publisher..These findings suggest that LEF-1 might play an important role in colon carcinogenesis by acting as a regulator. Enhanced expression of LEF-1-FL, which occurs frequently in colon cancer, may be a new target for clinical therapy. ..
- Hovanes K, Li T, Munguia J, Truong T, Milovanovic T, Lawrence Marsh J, et al. Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet. 2001;28:53-7 pubmed..allowing it to accumulate in the nucleus and form complexes with any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to ..
- Filali M, Cheng N, Abbott D, Leontiev V, Engelhardt J. Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter. J Biol Chem. 2002;277:33398-410 pubmed..In summary, these results provide evidence for transcriptional regulation of the LEF-1 promoter by Wnt and enhance the mechanistic understanding of Wnt/beta-catenin signaling in the regulation of LEF-1-dependent developmental processes. ..
- Porfiri E, Rubinfeld B, Albert I, Hovanes K, Waterman M, Polakis P. Induction of a beta-catenin-LEF-1 complex by wnt-1 and transforming mutants of beta-catenin. Oncogene. 1997;15:2833-9 pubmed..The analysis of several cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 protein with beta-catenin...
- van Genderen C, Okamura R, Farinas I, Quo R, Parslow T, Bruhn L, et al. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 1994;8:2691-703 pubmed..Together, the pattern of these defects suggest an essential role for LEF-1 in the formation of several organs and structures that require inductive tissue interactions. ..
- Huang F, Chen Y, Chang C, Yuan R, Jeng Y. Hepatocyte growth factor activates Wnt pathway by transcriptional activation of LEF1 to facilitate tumor invasion. Carcinogenesis. 2012;33:1142-8 pubmed publisher..Lymphoid-enhancing factor 1 (LEF1) is a transcription factor mediating Wnt/?-catenin signaling...
- Amen M, Liu X, Vadlamudi U, Elizondo G, Diamond E, Engelhardt J, et al. PITX2 and beta-catenin interactions regulate Lef-1 isoform expression. Mol Cell Biol. 2007;27:7560-73 pubmed..These data support a role for PITX2 in cell proliferation, migration, and cell division through differential Lef-1 isoform expression and interactions with Lef-1 and beta-catenin. ..
- Waterman M. Lymphoid enhancer factor/T cell factor expression in colorectal cancer. Cancer Metastasis Rev. 2004;23:41-52 pubmed..While the underlying mechanism for a change in the LEF/TCF isoform expression is not yet known, recent evidence implicates the Wnt signaling pathway itself as a potential modulator. ..
- Holnthoner W, Pillinger M, Groger M, Wolff K, Ashton A, Albanese C, et al. Fibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human endothelial cells. J Biol Chem. 2002;277:45847-53 pubmed..In conclusion, FGF-2 is a novel modulator of Lef/Tcf-beta-catenin signaling in endothelial cells, suggesting that angiogenic properties of FGF-2 are at least in part mediated by Lef/Tcf-beta-catenin activation. ..
- Kahler R, Westendorf J. Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J Biol Chem. 2003;278:11937-44 pubmed..A functional binding site for the high mobility group protein lymphoid enhancer-binding factor 1 (LEF1) was found adjacent to the proximal Runx2-binding site in the osteocalcin promoter...
- Gandhirajan R, Staib P, Minke K, Gehrke I, Plickert G, Schlösser A, et al. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Neoplasia. 2010;12:326-35 pubmed..We have demonstrated that targeting lef-1 is a new and selective therapeutic approach in CLL. CGP049090 or PKF115-584 may be attractive compounds for CLL and other malignancies that deserve further (pre)clinical evaluation. ..
- Shelton D, Fornalik H, Neff T, Park S, Bender D, Degeest K, et al. The role of LEF1 in endometrial gland formation and carcinogenesis. PLoS ONE. 2012;7:e40312 pubmed publisher..We hypothesized that Lef1 is required for endometrial gland formation within the uterus and is overexpressed in endometrial cancer...
- Petropoulos K, Arseni N, Schessl C, Stadler C, Rawat V, Deshpande A, et al. A novel role for Lef-1, a central transcription mediator of Wnt signaling, in leukemogenesis. J Exp Med. 2008;205:515-22 pubmed publisher..These data indicate a thus far unknown role of Lef-1 in the biology of acute leukemia, pointing to the necessity of balanced Lef-1 expression for an ordered hematopoietic development. ..
- Cianferotti L, Cox M, Skorija K, Demay M. Vitamin D receptor is essential for normal keratinocyte stem cell function. Proc Natl Acad Sci U S A. 2007;104:9428-33 pubmed..Transient gene expression assays demonstrate that the cooperative transcriptional effects of beta-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical ..
- Luderer H, Gori F, Demay M. Lymphoid enhancer-binding factor-1 (LEF1) interacts with the DNA-binding domain of the vitamin D receptor. J Biol Chem. 2011;286:18444-51 pubmed publisher..A novel interaction between the VDR and LEF1 (lymphoid enhancer-binding factor-1) that is independent of ?-catenin was identified...
- Milatovich A, Travis A, Grosschedl R, Francke U. Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf. Genomics. 1991;11:1040-8 pubmed..The location of the LEF1 gene on human and mouse chromosomes was determined by Southern blot analysis of DNA from panels of interspecies ..
- Han L, Liu B, Chen X, Chen H, Deng W, Yang C, et al. Activation of Wnt/?-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in in vitro culture model. Lasers Med Sci. 2018;33:637-645 pubmed publisher..Immunofluorescence staining was performed to assess the expression of ?-catenin, GSK3?, p-GSK3?, and Lef1 in the Wnt/?-catenin signaling...
- Zeng Y, Shen Z, Gu W, Wu M. Inhibition of hepatocellular carcinoma tumorigenesis by curcumin may be associated with CDKN1A and CTGF. Gene. 2018;651:183-193 pubmed publisher..Finally, we detected the expression of CDKN1A, CTGF, LEF1 TF and MIR-19A regulated by curcumin in PLC/PRF/5 cells using RT-PCR...
- Kundu A, Khouri M, Aryana S, Firestone G. 1-Benzyl-indole-3-carbinol is a highly potent new small molecule inhibitor of Wnt/?catenin signaling in melanoma cells that coordinately inhibits cell proliferation and disrupts expression of Microphthalmia Associated Transcription Factor isoform M. Carcinogenesis. 2017;: pubmed publisher..1-Benzyl I3C ablated Wnt-activated LEF1-dependent reporter gene activity in a TOP FLASH assay that was rescued by expression of a constitutively active ..
- Schmitt A, Griffith C, Cohen C, Siddiqui M. LEF-1: Diagnostic utility in distinguishing basaloid neoplasms of the salivary gland. Diagn Cytopathol. 2017;45:1078-1083 pubmed publisherb>Lymphoid enhancer binding factor 1 (LEF-1) has recently been reported as a potential immunohistochemical (IHC) marker for basal cell adenoma (BCA) and other salivary gland tumors, which may contribute to an increased accuracy in ..
- Hoepfner J, Kleinsorge M, Papp O, Ackermann M, Alfken S, Rinas U, et al. Biphasic modulation of Wnt signaling supports efficient foregut endoderm formation from human pluripotent stem cells. Cell Biol Int. 2016;40:534-48 pubmed publisher..reporter construct that enabled robust T-cell transcription factor 4 (TCF4)/lymphoid enhancer-binding factor 1 (LEF1)-mediated luciferase expression in differentiating pluripotent stem cells...
- Kermanshahi T, Jayachandran P, Chang D, Pai R. LEF-1 is frequently expressed in colorectal carcinoma and not in other gastrointestinal tract adenocarcinomas: an immunohistochemical survey of 602 gastrointestinal tract neoplasms. Appl Immunohistochem Mol Morphol. 2014;22:728-34 pubmed publisher..LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma. ..
- Liang J, Li Y, Daniels G, Sfanos K, De Marzo A, Wei J, et al. LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a. Mol Cancer Res. 2015;13:681-8 pubmed publisher..Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt signaling pathway, and has been suggested to be involved in regulation of ..
- Nikuseva Martic T, Serman L, Zeljko M, Vidas Z, Gasparov S, Zeljko H, et al. Expression of secreted frizzled-related protein 1 and 3, T-cell factor 1 and lymphoid enhancer factor 1 in clear cell renal cell carcinoma. Pathol Oncol Res. 2013;19:545-51 pubmed publisher..The TCF1 expression level was significantly weaker in normal tissue compared to tumor samples while LEF1 protein levels were significantly weaker in tumor tissue...
- DrÃ¤ger J, Simon Keller K, Pukrop T, Klemm F, Wilting J, Sticht C, et al. LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma. Oncotarget. 2017;8:3259-3273 pubmed publisher..We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness ..
- Kim D, You E, Jeong J, Ko P, Kim J, Rhee S. DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening. Sci Rep. 2017;7:6847 pubmed publisher..Promoter analysis and chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for DDR2 induction during cell culture on a stiff matrix...
- Béland M, Pilon N, Houle M, Oh K, Sylvestre J, Prinos P, et al. Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex. Mol Cell Biol. 2004;24:5028-38 pubmed..However, this region is devoid of a demonstrable Cdx response element(s). We have now found that Cdx1 and LEF1, a nuclear effector of Wnt signaling, synergize to induce expression from the Cdx1 promoter through previously ..
- Hamada F, Bienz M. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell. 2004;7:677-85 pubmed..Our evidence indicates that APC is an adaptor between beta-catenin and CtBP and that CtBP lowers the availability of free nuclear beta-catenin for binding to TCF by sequestering APC/beta-catenin complexes. ..
- El Tanani M, Platt Higgins A, Rudland P, Campbell F. Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription. J Biol Chem. 2004;279:20794-806 pubmed..These results suggest that the presence of these transcription factors in human breast cancer is responsible in part for the overexpression of OPN that, in turn, is implicated in mammary neoplastic progression and metastasis. ..
- Bagga R, Emerson B. An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro. Genes Dev. 1997;11:629-39 pubmed..Thus, long-range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity. ..