Sox4 stimulates β-catenin activity through induction of CK2

Abstract

β-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of β-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances β-catenin/TCF activity by increasing the stability of β-catenin. Sox4 increased the protein level of β-catenin and its target gene cyclin D1 in a dose-dependent manner. An siRNA experiment for Sox4 also demonstrated that Sox4 increases the protein levels of β-catenin and thus activates the Wnt signaling pathway. We found that induction of β-catenin/TCF activity by Sox4 is caused by stabilization of the β-catenin protein, but not by induction of β-catenin transcription. We further demonstrate that the increased level of β-catenin is caused by induction of CK2. In light of recent evidence that Sox4 expression is activated in the colon and in other tumors with β-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.