High β-catenin/Tcf-4 activity confers glioma progression via direct regulation of AKT2 gene expression.

Recent data suggest that the β-catenin/Tcf-4 signaling pathway plays an important role in human cancer tumorigenesis. However, the mechanism of β-catenin/Tcf-4 signaling in tumorigenesis is poorly understood. In this study, we show that Tcf-4 protein levels were significantly elevated in high-grade gliomas in comparison with low-grade gliomas and that Tcf-4 levels correlated with levels of AKT2. Reduction of β-catenin/Tcf-4 activity inhibited glioma cell proliferation and invasion in vitro and tumor growth in vivo. This effect of β-catenin/Tcf-4 activity was mediated by AKT2, and in vivo binding of β-catenin/Tcf-4 to the AKT2 promoter was validated using the chromatin immunoprecipitation assay and luciferase reporter assays. Taken together, we have demonstrated that Tcf-4 is associated with glioma progression and that AKT2 is a new member of the genes that are regulated by β-catenin/Tcf-4.