Sox4 stimulates β-catenin activity through induction of CK2

beta-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of beta-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances beta-catenin/TCF activity by increasing the stability of beta-catenin. Sox4 increased the protein level of beta-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 beta-catenin and thus activates the Wnt signaling pathway. We found that induction of beta-catenin/TCF activity by Sox4 is caused by stabilization of the beta-catenin protein, but not by induction of beta-catenin transcription. We further demonstrate that the increased level of beta-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 beta-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.