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

被引：1728

作者：

van de Wetering, M

Sancho, E

Verweij, C

de Lau, W

Oving, I

Hurlstone, A

van der Horn, K

Batlle, E

Coudreuse, D

Haramis, AP

Tion-Pon-Fong, M

Moerer, P

van den Born, M

Soete, G

Pals, S

Eilers, M

Medema, R

Clevers, H

机构：

[1] Univ Med Ctr, Dept Immunol, NL-3584 CX Utrecht, Netherlands

[2] Univ Med Ctr, Ctr Biomed Genet, NL-3584 CX Utrecht, Netherlands

[3] VU Med Ctr, Dept Mol Cellular Biol, NL-1081 BT Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands

[5] Inst Mol Biol & Tumor Res, D-35033 Marburg, Germany

[6] Netherlands Canc Inst, Dept Mol Biol, NL-1066 CX Amsterdam, Netherlands

来源：

CELL | 2002年 / 111卷 / 02期

关键词：

D O I：

10.1016/S0092-8674(02)01014-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transactivation of TCF target genes induced by Writ 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.

引用

页码：241 / 250

页数：10

共 51 条

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