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1: J Biol Chem. 2005 Mar 25;280(12):11740-8. Epub 2005 Jan 11.
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Wnt-dependent regulation of the E-cadherin repressor snail.

Yook JI, Li XY, Ota I, Fearon ER, Weiss SJ.

Department of Oral Pathology, BK21 Project for Medical Science, College of Dentistry, Yonsei University, Seoul 120-742, Korea.

Down-regulation of E-cadherin marks the initiation of the epithelial-mesenchymal transition, a process exploited by invasive cancer cells. The zinc finger transcription factor, Snail, functions as a potent repressor of E-cadherin expression that can, acting alone or in concert with the Wnt/beta-catenin/T cell factor axis, induce an epithelial-mesenchymal transition. Although mechanisms that coordinate signaling events initiated by Snail and Wnt remain undefined, we demonstrate that Snail displays beta-catenin-like canonical motifs that support its GSK3beta-dependent phosphorylation, beta-TrCP-directed ubiquitination, and proteasomal degradation. Accordingly, Wnt signaling inhibits Snail phosphorylation and consequently increases Snail protein levels and activity while driving an in vivo epithelial-mesenchymal transition that is suppressed following Snail knockdown. These findings define a potential mechanism whereby Wnt signaling stabilizes Snail and beta-catenin proteins in tandem fashion so as to cooperatively engage transcriptional programs that control an epithelial-mesenchymal transition.

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PMID: 15647282 [PubMed - indexed for MEDLINE]