Snail promotes Wnt target gene expression and interacts with beta-catenin.

The transcription factor snail represses epithelial gene expression and thereby promotes epithelial-mesenchymal transitions (EMT) and tumor invasion. The Wnt/beta-catenin pathway is also involved in EMT and was shown to activate snail. Here, we demonstrate that snail increases Wnt reporter gene activity induced by beta-catenin, LRP6 or dishevelled, and also promotes transcription activated by GAL4-beta-catenin fusion proteins. Snail mutants lacking the transcriptional repressor domain also stimulate beta-catenin-dependent transcription indicating that downregulation of snail target genes is not required for this activity. Snail interacts with beta-catenin in immunoprecipitation experiments at its N-terminus, which is required for activation by snail. In colorectal cancer cell lines, overexpression of snail leads to increased expression of Wnt target genes, whereas downregulation of endogenous snail by siRNA reduces target gene expression. Our data indicate a positive feedback stimulation of the Wnt pathway by activation of snail.