The beta-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 beta-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 › Academic › peer-review

Abstract

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

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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/S0092-8674(02)01014-0

Cite this

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 beta-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{22b38d69421240288527613ece3e0838,

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

abstract = "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",

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",

year = "2002",

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

language = "English",

volume = "111",

pages = "241--250",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "2",

}

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 beta-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 beta-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

Y1 - 2002

N2 - 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

AB - 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

U2 - 10.1016/S0092-8674(02)01014-0

DO - 10.1016/S0092-8674(02)01014-0

M3 - Article

C2 - 12408868

SN - 0092-8674

VL - 111

SP - 241

EP - 250

JO - Cell

JF - Cell

IS - 2

ER -

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

Abstract

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