The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
Cell
; 111(2): 241-50, 2002 Oct 18.
Article
en En
| MEDLINE
| ID: mdl-12408868
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.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Neoplasias Colorrectales
/
Transactivadores
/
Proteínas del Citoesqueleto
/
Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2002
Tipo del documento:
Article
País de afiliación:
Países Bajos