Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Oct 18;111(2):241-50.
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  1 , 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
Affiliations
Free article

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

Marc van de Wetering et al. Cell. .
Free article

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Novel immunotherapeutics against LGR5 to target multiple cancer types.
    Chen HC, Mueller N, Stott K, Kapeni C, Rivers E, Sauer CM, Beke F, Walsh SJ, Ashman N, O'Brien L, Rafati Fard A, Godsinia A, Li C, Joud F, Giger O, Zlobec I, Olan I, Aitken SJ, Hoare M, Mair R, Serrao E, Brenton JD, Garcia-Gimenez A, Richardson SE, Huntly B, Spring DR, Skjoedt MO, Skjødt K, de la Roche M, de la Roche M. Chen HC, et al. EMBO Mol Med. 2024 Aug 21. doi: 10.1038/s44321-024-00121-2. Online ahead of print. EMBO Mol Med. 2024. PMID: 39169164
  • Cell competition in primary and metastatic colorectal cancer.
    van Luyk ME, Krotenberg Garcia A, Lamprou M, Suijkerbuijk SJE. van Luyk ME, et al. Oncogenesis. 2024 Jul 26;13(1):28. doi: 10.1038/s41389-024-00530-5. Oncogenesis. 2024. PMID: 39060237 Free PMC article. Review.
  • Host-microbiota interaction in intestinal stem cell homeostasis.
    Wu H, Mu C, Xu L, Yu K, Shen L, Zhu W. Wu H, et al. Gut Microbes. 2024 Jan-Dec;16(1):2353399. doi: 10.1080/19490976.2024.2353399. Epub 2024 May 17. Gut Microbes. 2024. PMID: 38757687 Free PMC article. Review.
  • Tissue and cellular spatiotemporal dynamics in colon aging.
    Daly AC, Cambuli F, Äijö T, Lötstedt B, Marjanovic N, Kuksenko O, Smith-Erb M, Fernandez S, Domovic D, Van Wittenberghe N, Drokhlyansky E, Griffin GK, Phatnani H, Bonneau R, Regev A, Vickovic S. Daly AC, et al. bioRxiv [Preprint]. 2024 Apr 26:2024.04.22.590125. doi: 10.1101/2024.04.22.590125. bioRxiv. 2024. PMID: 38712088 Free PMC article. Preprint.
  • A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells.
    Han Y, Sun K, Yu S, Qin Y, Zhang Z, Luo J, Hu H, Dai L, Cui M, Jiang C, Liu F, Huang Y, Gao P, Chen X, Xin T, Ren X, Wu X, Song J, Wang Q, Tang Z, Chen J, Zhang H, Zhang X, Liu M, Luo D. Han Y, et al. EMBO J. 2024 May;43(10):1990-2014. doi: 10.1038/s44318-024-00082-9. Epub 2024 Apr 11. EMBO J. 2024. PMID: 38605226 Free PMC article.
See all "Cited by" articles

Publication types

MeSH terms

-