TY - JOUR
T1 - The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells
AU - Van de Wetering, Marc
AU - Sancho, Elena
AU - Verweij, Cornelis
AU - De Lau, Wim
AU - Oving, Irma
AU - Hurlstone, Adam
AU - Van der Horn, Karin
AU - Batlle, Eduard
AU - Coudreuse, Damien
AU - Haramis, Anna Pavlina
AU - Tjon-Pon-Fong, Menno
AU - Moerer, Petra
AU - Van den Born, Maaike
AU - Soete, Gwen
AU - Pals, Steven
AU - Eilers, Martin
AU - Medema, Rene
AU - Clevers, Hans
PY - 2002/10/18
Y1 - 2002/10/18
N2 - 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 β-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 p21CIP1/WAF1 promoter. Following disruption of β-catenin/TCF-4 activity, the decreased expression of c-MYC releases p21CIP1/WAF1 transcription, which in turn mediates G1 arrest and differentiation. Thus, the β-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells.
AB - 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 β-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 p21CIP1/WAF1 promoter. Following disruption of β-catenin/TCF-4 activity, the decreased expression of c-MYC releases p21CIP1/WAF1 transcription, which in turn mediates G1 arrest and differentiation. Thus, the β-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells.
U2 - 10.1016/S0092-8674(02)01014-0
DO - 10.1016/S0092-8674(02)01014-0
M3 - Article
C2 - 12408868
SN - 1097-4172
VL - 111
SP - 241
EP - 250
JO - Cell
JF - Cell
IS - 2
ER -
