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

Marc Van de Wetering; 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

doi:10.1016/S0092-8674(02)01014-0

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

Marc Van de Wetering, 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

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Pages (from-to)	241-250
Number of pages	9
Journal	Cell
Volume	111
Issue number	2
DOIs	https://doi.org/10.1016/S0092-8674(02)01014-0
Publication status	Published - 18 Oct 2002

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Van de Wetering, M., Sancho, E., Verweij, C., De Lau, W., Oving, I., Hurlstone, A., Van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A. P., Tjon-Pon-Fong, M., Moerer, P., Van den Born, M., Soete, G., Pals, S., Eilers, M., Medema, R., & Clevers, H. (2002). The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell, 111(2), 241-250. https://doi.org/10.1016/S0092-8674(02)01014-0

@article{5d5a6c7ac03d4f2284101d7b54582c03,

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

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 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.",

author = "{Van de Wetering}, Marc and Elena Sancho and Cornelis Verweij and {De Lau}, Wim and Irma Oving and Adam Hurlstone and {Van der Horn}, Karin and Eduard Batlle and Damien Coudreuse and Haramis, {Anna Pavlina} and Menno Tjon-Pon-Fong and Petra Moerer and {Van den Born}, Maaike and Gwen Soete and Steven Pals and Martin Eilers and Rene Medema and Hans Clevers",

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doi = "10.1016/S0092-8674(02)01014-0",

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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, Tjon-Pon-Fong, M, Moerer, P, Van den Born, M, Soete, G, Pals, S, Eilers, M, Medema, R & Clevers, H 2002, 'The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells', Cell, vol. 111, no. 2, pp. 241-250. https://doi.org/10.1016/S0092-8674(02)01014-0

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 -

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

Abstract

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