CXCR4 promotes GSK3β expression in pancreatic cancer cells via the Akt pathway

CXCR4 and glycogen synthase kinase-3 beta (GSK3 beta) promote proliferation and invasion of pancreatic cancer. Inhibition of CXCR4 suppresses GSK3 beta expression. However, the molecular mechanism by which CXCR4 contributes to human pancreatic cancer metastasis is not completely understood. In this study, therefore, we analyzed the effect of CXCR4 on GSK3 beta expression and its molecular mechanism. PANC-1 and SW-1990 cells were used in this study. PANC-1 and SW-1990 cell lines which stably expressed upregulated or downregulated CXCR4 were used for further study. Western blotting was employed to detected the expression of CXCR4, GSK3 beta and MMP-2. Cell invasion assay was used to detect the effect of the Akt pathway on CXCR4-induced GSK3 beta expression. Overexpression of CXCR4 promoted GSK3 beta expression and silencing of CXCR4 suppressed GSK3 beta expression. Overexpression of CXCR4 activated cyclin D1 and p-Akt expression, but inhibited p21 expression. Silencing of CXCR4 had the reverse effect. CXCR4 promoted GSK3 beta expression and PANC-1 invasion by Akt signaling. CXCR4 upregulated GSK3 beta expression, at least in part, at the level of transcription. CXCR4 promotes GSK3 beta expression via the Akt cell signaling pathway in pancreatic cancer cells.