lymphoid enhancer binding factor 1


Summary: A T-cell factor that plays an essential role in EMBRYONIC DEVELOPMENT.

Top Publications

  1. Hoeppner L, Secreto F, Jensen E, Li X, Kahler R, Westendorf J. Runx2 and bone morphogenic protein 2 regulate the expression of an alternative Lef1 transcript during osteoblast maturation. J Cell Physiol. 2009;221:480-9 pubmed publisher
    ..Taken together, our results suggest Lef1DeltaN is a crucial regulator of terminal differentiation in osseous cells. ..
  2. Chen J, Lan Y, Baek J, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009;334:174-85 pubmed publisher
    ..Together, these results indicate that activation of the mesenchymal odontogenic program during early tooth development requires concerted actions of Bmp, Fgf and Wnt signaling from the presumptive dental epithelium to the mesenchyme...
  3. Yun K, So J, Jash A, Im S. Lymphoid enhancer binding factor 1 regulates transcription through gene looping. J Immunol. 2009;183:5129-37 pubmed publisher
    ..We have previously shown that IL-1beta-induced lymphoid enhancer binding factor 1 (Lef1) regulates the transcription of its target genes COX2 and MMP13 in mouse chondrocytes by ..
  4. Noh T, Gabet Y, Cogan J, Shi Y, Tank A, Sasaki T, et al. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. PLoS ONE. 2009;4:e5438 pubmed publisher
    ..The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice. ..
  5. Jensen E, Gopalakrishnan R, Westendorf J. Regulation of gene expression in osteoblasts. Biofactors. 2010;36:25-32 pubmed publisher
  6. Skokowa J, Welte K. Dysregulation of myeloid-specific transcription factors in congenital neutropenia. Ann N Y Acad Sci. 2009;1176:94-100 pubmed publisher
  7. 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. ..
  8. Zhang C, Jia Z, Li B, Zhang H, Liu Y, Chen P, et al. beta-Catenin/TCF/LEF1 can directly regulate phenylephrine-induced cell hypertrophy and Anf transcription in cardiomyocytes. Biochem Biophys Res Commun. 2009;390:258-62 pubmed publisher
    ..Thus, we document a direct positive role of beta-catenin on PE-induced cardiomyocyte hypertrophy and identify a new target gene for beta-catenin/TCF/LEF1. ..
  9. Sasaki H, Muramatsu T, Kwon H, Yamamoto H, Hashimoto S, Jung H, et al. Down-regulated genes in mouse dental papillae and pulp. J Dent Res. 2010;89:679-83 pubmed publisher
    ..These results suggest that down-regulation of these three genes is an important factor in normal odontogenesis in dental papillae. ..

More Information


  1. Tian H, Lv P, Ma K, Zhou C, Gao X. Beta-catenin/LEF1 activated enamelin expression in ameloblast-like cells. Biochem Biophys Res Commun. 2010;398:519-24 pubmed publisher
    ..The results suggested that Wnt/beta-catenin signaling could function in enamelin gene expression by direct interaction through two conserved LEF1 responsive elements on the enamelin gene in ameloblast-like cells. ..
  2. Beagle B, Johnson G. Differential modulation of TCF/LEF-1 activity by the soluble LRP6-ICD. PLoS ONE. 2010;5:e11821 pubmed publisher
    ..These results suggest that LRP6-ICD can differentially modulate Wnt pathway transcriptional activity depending upon its subcellular localization and differential protein-protein interactions. ..
  3. Fujimori S, Novak H, Weissenböck M, Jussila M, Gonçalves A, Zeller R, et al. Wnt/?-catenin signaling in the dental mesenchyme regulates incisor development by regulating Bmp4. Dev Biol. 2010;348:97-106 pubmed publisher
    ..This provides a mechanism whereby the number of incisors arising from one placode can be varied through local alterations of a mesenchymal signaling circuit involving ?-catenin, Lef1, Tcf1 and Bmp4. ..
  4. Dieudonné F, Marion A, Hay E, Marie P, Modrowski D. High Wnt signaling represses the proapoptotic proteoglycan syndecan-2 in osteosarcoma cells. Cancer Res. 2010;70:5399-408 pubmed publisher
    ..Our results identify syndecan-2 as a Wnt target and bring new insights into a possible pathologic role of Wnt signaling in osteosarcoma. ..
  5. Royer Pokora B, Busch M, Beier M, Duhme C, de Torres C, Mora J, et al. Wilms tumor cells with WT1 mutations have characteristic features of mesenchymal stem cells and express molecular markers of paraxial mesoderm. Hum Mol Genet. 2010;19:1651-68 pubmed publisher
    ..We conclude that WTs with WT1 mutations have specific traits of PAM, which is the source of kidney stromal cells. ..
  6. Yasuhara R, Yuasa T, Williams J, Byers S, Shah S, Pacifici M, et al. Wnt/beta-catenin and retinoic acid receptor signaling pathways interact to regulate chondrocyte function and matrix turnover. J Biol Chem. 2010;285:317-27 pubmed publisher
    ..Taken together, our data indicate that the Wnt and retinoid signaling pathways do interact in chondrocytes, and their cross-talks and cross-regulation play important roles in the regulation of cartilage matrix homeostasis. ..
  7. Mittelman M, Oster H, Hoffman M, Neumann D. The lower risk MDS patient at risk of rapid progression. Leuk Res. 2010;34:1551-5 pubmed publisher
    ..5q-), high level of methylation of other genes, absence of the TET2 mutation, down regulation of the lymphoid enhancer binding factor 1 (LEF1), mutation of the polycomb-associated gene ASXL1 and a specific 6-gene signature in gene ..
  8. Lu D, Liu J, Endo T, Zhou H, Yao S, Willert K, et al. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway. PLoS ONE. 2009;4:e8294 pubmed publisher
    ..Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/beta-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease. ..
  9. 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
    ..This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis. ..
  10. Liu X, Luo M, Xie W, Wells J, Goodheart M, Engelhardt J. Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter. Am J Physiol Lung Cell Mol Physiol. 2010;299:L694-710 pubmed publisher
  11. Liu B, Rooker S, Helms J. Molecular control of facial morphology. Semin Cell Dev Biol. 2010;21:309-13 pubmed publisher
  12. Gehrke I, Gandhirajan R, Kreuzer K. Targeting the WNT/beta-catenin/TCF/LEF1 axis in solid and haematological cancers: Multiplicity of therapeutic options. Eur J Cancer. 2009;45:2759-67 pubmed publisher
    ..Furthermore, we discuss the possible strategies to target this pathway and their potential importance in cancer treatment. ..
  13. Zhang Z, Florez S, Gutierrez Hartmann A, Martin J, Amendt B. MicroRNAs regulate pituitary development, and microRNA 26b specifically targets lymphoid enhancer factor 1 (Lef-1), which modulates pituitary transcription factor 1 (Pit-1) expression. J Biol Chem. 2010;285:34718-28 pubmed publisher
  14. 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
    ..LEF1 is highly expressed in androgen-independent prostate cancer, potentially serving as a marker for androgen-independent disease. ..
  15. Dasgupta C, Sakurai R, Wang Y, Guo P, Ambalavanan N, Torday J, et al. Hyperoxia-induced neonatal rat lung injury involves activation of TGF-{beta} and Wnt signaling and is protected by rosiglitazone. Am J Physiol Lung Cell Mol Physiol. 2009;296:L1031-41 pubmed publisher
    ..Administration of PPARgamma agonists may thus be a potential strategy to attenuate hyperoxia-induced lung injury and subsequent BPD. ..
  16. Westenskow P, Piccolo S, Fuhrmann S. Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development. 2009;136:2505-10 pubmed publisher
  17. Yu W, Ruest L, Svoboda K. Regulation of epithelial-mesenchymal transition in palatal fusion. Exp Biol Med (Maywood). 2009;234:483-91 pubmed publisher
    ..The roles and interactions among these transcription factors will be discussed. ..
  18. Xu H, McCann M, Zhang Z, Posner G, Bingham V, El Tanani M, et al. Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals. Mol Carcinog. 2009;48:758-72 pubmed publisher
    ..These findings may be relevant to the cell- or tissue-specificity of vitamin D growth regulation. ..
  19. Tetzlaff S, Jonas E, Phatsara C, Murani E, Ponsuksili S, Schellander K, et al. Evidence for association of lymphoid enhancer-binding factor-1 (LEF1) with the number of functional and inverted teats in pigs. Cytogenet Genome Res. 2009;124:139-46 pubmed publisher
    ..06) in the experimental DUMI population. The function, position, and associations shown here promote LEF1 as a candidate gene for number of teats and in particular for presence and number of inverted teats. ..
  20. Sutton G, Madigan M, Roufas A, McAvoy J. Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clin Exp Ophthalmol. 2010;38:43-8 pubmed publisher
    ..Future investigations are required to establish if SFRP1 may be a potential marker of KC progression or if manipulation of its expression can be used to therapeutic effect in this disease. ..
  21. Chen Q, Zhang T, Pincus S, Wu S, Ricks D, Liu D, et al. Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements. J Immunol. 2010;184:5047-54 pubmed publisher
    ..Our finding links LEF-1 to CD1D and suggests a role of Wnt signaling in the regulation of the human CD1D gene. ..
  22. 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. ..
  23. Tian X, Li J, Ma Z, Zhao C, Wan D, Wen Y. Role of hepatitis B surface antigen in the development of hepatocellular carcinoma: regulation of lymphoid enhancer-binding factor 1. J Exp Clin Cancer Res. 2009;28:58 pubmed publisher
    ..It is speculated that HBsAg could stimulate proliferation and functional modification of hepatocytes via LEF-1 through the Wnt pathway at the pre-malignant stage. ..
  24. Iwai L, Kawasaki H. Molecular development of the lateral geniculate nucleus in the absence of retinal waves during the time of retinal axon eye-specific segregation. Neuroscience. 2009;159:1326-37 pubmed publisher
    ..Our results suggest that LGN development proceeds, at least in part, even in the absence of retinal inputs. PCP4, TCF7L2 and Lhx9 should be useful to examine LGN development during eye-specific segregation in mice and in ferrets...
  25. Stover J, Shi J, Jin W, Vogt P, Boger D. Discovery of inhibitors of aberrant gene transcription from Libraries of DNA binding molecules: inhibition of LEF-1-mediated gene transcription and oncogenic transformation. J Am Chem Soc. 2009;131:3342-8 pubmed publisher
  26. Medici D, Nawshad A. Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-kappaB and LEF-1. Matrix Biol. 2010;29:161-5 pubmed publisher
    ..These data provide a foundation for understanding the mechanisms by which collagen I stimulates EMT and identify potential therapeutic targets for suppressing this transition in pathological conditions. ..
  27. Kim M, Kim H, Jho E. Identification of ptpro as a novel target gene of Wnt signaling and its potential role as a receptor for Wnt. FEBS Lett. 2010;584:3923-8 pubmed publisher
    ..In addition, ectopic expression of this extracellular domain inhibited Wnt-mediated reporter activity. These results suggest that ptpro is a target gene of Wnt/?-catenin signaling and that PTPRO may function as a novel receptor for Wnt. ..
  28. Yochum G, Sherrick C, MacPartlin M, Goodman R. A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers. Proc Natl Acad Sci U S A. 2010;107:145-50 pubmed publisher
    ..Thus, we propose that a distinct chromatin architecture coordinated by beta-catenin/TCF-bound WREs accompanies transcriptional activation of MYC gene expression. ..
  29. Shi F, Cheng Y, Wang X, Edge A. Beta-catenin up-regulates Atoh1 expression in neural progenitor cells by interaction with an Atoh1 3' enhancer. J Biol Chem. 2010;285:392-400 pubmed publisher
  30. Hebenstreit D, Giaisi M, Treiber M, Zhang X, Mi H, Horejs Hoeck J, et al. LEF-1 negatively controls interleukin-4 expression through a proximal promoter regulatory element. J Biol Chem. 2008;283:22490-7 pubmed publisher
    ..Furthermore, we found that IL-4 stimulation possesses a negative effect on the expressions of LEF-1 and TCF-1 in primary T cells, suggesting a positive feedback effect of IL-4 on IL4 gene expression. ..
  31. Taniguchi N, Caramés B, Kawakami Y, Amendt B, Komiya S, Lotz M. Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathway. Proc Natl Acad Sci U S A. 2009;106:16817-22 pubmed publisher
    ..Loss of the HMGB2-Wnt signaling interaction is a new mechanism in aging-related cartilage pathology. ..
  32. Handrigan G, Richman J. A network of Wnt, hedgehog and BMP signaling pathways regulates tooth replacement in snakes. Dev Biol. 2010;348:130-41 pubmed publisher
  33. Mazumdar J, O Brien W, Johnson R, Lamanna J, Chavez J, Klein P, et al. O2 regulates stem cells through Wnt/?-catenin signalling. Nat Cell Biol. 2010;12:1007-13 pubmed publisher
    ..This decline correlates with reduced Wnt/?-catenin signalling in the subgranular zone. O2 availability, therefore, may have a direct role in stem cell regulation through HIF-1? modulation of Wnt/?-catenin signalling...
  34. 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
    ..For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. ..
  35. 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. ..
  36. Chen T, Li M, Ding Y, Zhang L, Xi Y, Pan W, et al. Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel Axin-interacting protein that activates Wnt/beta-catenin signaling. J Biol Chem. 2009;284:6683-9 pubmed publisher
    ..These results together indicate that Zbed3 is a novel Axin-binding protein that is involved in Wnt/beta-catenin signaling modulation. ..
  37. Tang Y, Simoneau A, Liao W, Yi G, Hope C, Liu F, et al. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells. Mol Cancer Ther. 2009;8:458-68 pubmed publisher
    ..These observations suggest a mechanism for transformation of bladder epithelium on loss of WIF1 function and provide new targets such as SKP2 for intervention in WIF1-deficient bladder cancer. ..
  38. Vendrell V, Summerhurst K, Sharpe J, Davidson D, Murphy P. Gene expression analysis of canonical Wnt pathway transcriptional regulators during early morphogenesis of the facial region in the mouse embryo. Gene Expr Patterns. 2009;9:296-305 pubmed publisher
  39. Wang S, Nan K, Wang Y. Endothelial cells promote the proliferation of lymphocytes partly through the Wnt pathway via LEF-1. Biochem Biophys Res Commun. 2009;388:67-72 pubmed publisher
    ..LEF-1 is one of the main molecular mediators in this process, and the inhibition of LEF-1 induces apoptosis. These results suggest that LEF-1 modulates positively the proliferation of lymphocytes induced by their interaction with ECs. ..
  40. Yokoyama N, Pate K, Sprowl S, Waterman M. A role for YY1 in repression of dominant negative LEF-1 expression in colon cancer. Nucleic Acids Res. 2010;38:6375-88 pubmed publisher
    ..We also show that induced expression of dnLEF-1 in colon cancer cells slows their rate of proliferation. We propose that YY1 plays an important role in preventing dnLEF-1 expression and growth inhibition in colon cancer. ..
  41. Wisniewska M, Misztal K, Michowski W, Szczot M, Purta E, Lesniak W, et al. LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain. J Neurosci. 2010;30:4957-69 pubmed publisher
    ..We propose that beta-catenin contributes to neuronal excitability not only by a local action at the synapse but also by activating gene expression in thalamic neurons. ..
  42. 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. ..
  43. Bucan V, Adili M, Choi C, Eddy M, Vogt P, Reimers K. Transactivation of lifeguard (LFG) by Akt-/LEF-1 pathway in MCF-7 and MDA-MB 231 human breast cancer cells. Apoptosis. 2010;15:814-21 pubmed publisher
    ..Our results therefore identify LFG as a target of the Akt/LEF-1 pathway in MDA-MB-231 breast tumour cells, a regulation which could play a key role in breast tumour progression. ..
  44. Humtsoe J, Liu M, Malik A, Wary K. Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures. Mol Cell Biol. 2010;30:1593-606 pubmed publisher
    ..Here, we tested the hypothesis that LPP3 stimulates beta-catenin/lymphoid enhancer binding factor 1 (beta-catenin/LEF-1) to induce EC migration and formation of branching point structures...
  45. Zhao D, Yu S, Zhou X, Haring J, Held W, Badovinac V, et al. Constitutive activation of Wnt signaling favors generation of memory CD8 T cells. J Immunol. 2010;184:1191-9 pubmed publisher
    ..Thus, constitutive activation of the canonical Wnt pathway favors memory CD8 T cell formation during initial immunization, resulting in enhanced immunity upon second encounter with the same pathogen. ..
  46. Navarro D, Agra N, Pestaña A, Alonso J, González Sancho J. The EWS/FLI1 oncogenic protein inhibits expression of the Wnt inhibitor DICKKOPF-1 gene and antagonizes beta-catenin/TCF-mediated transcription. Carcinogenesis. 2010;31:394-401 pubmed publisher
    ..Our results show that EWS/FLI1 inhibits both DKK-1 expression as well as beta-catenin/TCF-dependent transcription, which could contribute to progression of tumours of the Ewing family. ..
  47. Pellagatti A, Marafioti T, Paterson J, Malcovati L, Della Porta M, Jadersten M, et al. Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes. Br J Haematol. 2009;146:86-90 pubmed publisher
    ..Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS. ..
  48. Kaka A, Shaffer D, Hartmaier R, Hartmeier R, Leen A, Lu A, et al. Genetic modification of T cells with IL-21 enhances antigen presentation and generation of central memory tumor-specific cytotoxic T-lymphocytes. J Immunother. 2009;32:726-36 pubmed publisher
  49. Skokowa J, Fobiwe J, Dan L, Thakur B, Welte K. Neutrophil elastase is severely down-regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF-1. Blood. 2009;114:3044-51 pubmed publisher
    ..LEF-1 rescue of CD34(+) cells isolated from 2 patients with CN resulted in granulocytic differentiation of the cells which was in line with increased levels of functionally active ELA2/NE. ..
  50. Yang K, Jiang Z, Wang D, Lian X, Yang T. Corneal epithelial-like transdifferentiation of hair follicle stem cells is mediated by pax6 and beta-catenin/Lef-1. Cell Biol Int. 2009;33:861-6 pubmed publisher
    ..Bulge KSCs may have potential therapeutic application as cell source for the construction of bioengineered corneas...
  51. 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. ..
  52. Christova T, Mojtahedi G, Hamel P. Lymphoid enhancer factor-1 mediates loading of Pax3 to a promoter harbouring lymphoid enhancer factor-1 binding sites resulting in enhancement of transcription. Int J Biochem Cell Biol. 2010;42:630-40 pubmed publisher
    ..This mode of transcriptional regulation suggests further that Pax3 activity may directly effect the expression of factors regulated by signal transduction pathways dependent on Lef1. ..
  53. Abu Elmagd M, Robson L, Sweetman D, Hadley J, Francis West P, Munsterberg A. Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis. Dev Biol. 2010;337:211-9 pubmed publisher