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[Cancer Research 62, 5126-5128, September 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Wnt Signaling Regulates Expression of the Receptor Tyrosine Kinase Met in Colorectal Cancer1

Elles M. J. Boon, Ronald van der Neut, Marc van de Wetering, Hans Clevers and Steven T. Pals2

Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands [E. M. J. B., R. v. d. N., S. T. P.], and Department of Immunology and Center for Biomedical Genetics, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands [M. v. d. W., H. C.]

Overexpression of the receptor tyrosine kinase Met is an early event in the colorectal adenoma-carcinoma sequence. This suggests a link with disruption of adenomatous polyposis coli-controlled regulation of ß-catenin/T-cell factor (TCF)-mediated transcriptional activation, which is crucial in initiating tumorigenesis. Indeed, in intestinal biopsies from patients with familial adenomatous polyposis, we find Met already overexpressed in dysplastic aberrant crypt foci, the earliest neoplastic lesions of colorectal cancer (CRC). Moreover, in CRC cells, induction of dominant-negative TCF proteins and the consequent abrogation of ß-catenin/TCF-mediated transcriptional activation lead to a strong down-regulation of Met expression. Our results indicate that Met expression is part of a genetic program controlled by the Wnt pathway and suggest a role for Met in controlling the turnover and differentiation of intestinal epithelium.




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