Wnt signaling regulates expression of the receptor tyrosine kinase Met in colorectal cancer

Elles M.J. Boon, Ronald Van der Neut, Marc Van de Wetering, Hans Clevers, Steven T. Pals

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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 β-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 β-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.

Original languageEnglish
Pages (from-to)5126-5128
Number of pages3
JournalCancer Research
Issue number18
Publication statusPublished - 15 Sept 2002

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