The Intestinal Wnt/TCF Signature

L.G. van der Flier, J. Sabates-Bellver, I. Oving, A. Haegebarth, M. de Palo, M. Anti, M.E. van Gijn, S Suijkerbuijk, M. van de Wetering, G. Marra, J.C. Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

409 Citations (Scopus)

Abstract

BACKGROUND & AIMS: In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts. METHODS: We have now performed an exhaustive array-based analysis of this target gene program in colorectal cancer cell lines carrying an inducible block of the Wnt cascade. Independently, differential gene-expression profiles of human adenomas and adenocarcinomas vs normal colonic epithelium were obtained. RESULTS: Expression analyses of approximately 80 genes common between these data sets were performed in a murine adenoma model. The combined data sets describe a core target gene program, the intestinal Wnt/TCF signature gene set, which is responsible for the transformation of human intestinal epithelial cells. CONCLUSIONS: The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell.
Original languageEnglish
Pages (from-to)628-632
JournalGastroenterology
Volume132
Publication statusPublished - 2007

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