The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
Cell, 2002/10/18;111(2):241-50.
van de Wetering M[1], Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Batlle E, Coudreuse D, Haramis AP, Tjon-Pon-Fong M, Moerer P, van den Born M, Soete G, Pals S, Eilers M, Medema R, Clevers H
Affiliations
PMID: 12408868
Impact factor: 66.85
Abstract
The transactivation of TCF target genes induced by Wnt pathway mutations constitutes the primary transforming event in colorectal cancer (CRC). We show that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active in the proliferative compartment of colon crypts. Coincidently, an intestinal differentiation program is induced. The TCF-4 target gene c-MYC plays a central role in this switch by direct repression of the p21(CIP1/WAF1) promoter. Following disruption of beta-catenin/TCF-4 activity, the decreased expression of c-MYC releases p21(CIP1/WAF1) transcription, which in turn mediates G1 arrest and differentiation. Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells.
MeSH terms
Cell Cycle; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cytoskeletal Proteins; DNA-Binding Proteins; Humans; Intestinal Mucosa; Phenotype; Proto-Oncogene Proteins c-myc; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors; Tumor Cells, Cultured; beta Catenin
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