| Literature DB >> 12408868 |
Marc van de Wetering1, Elena Sancho, Cornelis Verweij, Wim de Lau, Irma Oving, Adam Hurlstone, Karin van der Horn, Eduard Batlle, Damien Coudreuse, Anna Pavlina Haramis, Menno Tjon-Pon-Fong, Petra Moerer, Maaike van den Born, Gwen Soete, Steven Pals, Martin Eilers, Rene Medema, Hans Clevers.
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.Entities:
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Year: 2002 PMID： 12408868 DOI： 10.1016/s0092-8674(02)01014-0
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582