Sox4 stimulates ß-catenin activity through induction of CK2.

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