The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells - PubMed (original) (raw)

. 2002 Oct 18;111(2):241-50.

doi: 10.1016/s0092-8674(02)01014-0.

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

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The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells

Marc van de Wetering et al. Cell. 2002.

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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.

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