Abstract
Background
CXCR4 and glycogen synthase kinase-3β (GSK3β) promote proliferation and invasion of pancreatic cancer. Inhibition of CXCR4 suppresses GSK3β 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 GSK3β expression and its molecular mechanism.
Methods
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, GSK3β and MMP-2. Cell invasion assay was used to detect the effect of the Akt pathway on CXCR4-induced GSK3β expression.
Results
Overexpression of CXCR4 promoted GSK3β expression and silencing of CXCR4 suppressed GSK3β expression. Overexpression of CXCR4 activated cyclin D1 and p-Akt expression, but inhibited p21 expression. Silencing of CXCR4 had the reverse effect. CXCR4 promoted GSK3β expression and PANC-1 invasion by Akt signaling. CXCR4 upregulated GSK3β expression, at least in part, at the level of transcription.
Conclusions
CXCR4 promotes GSK3β expression via the Akt cell signaling pathway in pancreatic cancer cells.
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Acknowledgments
This work was supported by the Innovation Team Fund of Huai’an First People’s Hospital, Nanjing Medical University.
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The authors declare that they have no conflict of interest.
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Ma, S., Li, Q. & Pan, F. CXCR4 promotes GSK3β expression in pancreatic cancer cells via the Akt pathway. Int J Clin Oncol 20, 525–530 (2015). https://doi.org/10.1007/s10147-014-0740-0
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DOI: https://doi.org/10.1007/s10147-014-0740-0