GSK3β mediates pancreatic cancer cell invasion in vitro via the CXCR4/MMP-2 Pathway

作者：Ying, Xu; Jing, Li; Ma, Shijie; Li, Qianjun; Luo, Xiaoling; Pan, Zhenguo; Feng, Yanling; Feng, Pan^*

来源：Cancer Cell International, 2015, 15(1): 70.

DOI：10.1186/s12935-015-0216-y

• Glycogen synthase kinase-3 beta (GSK3 beta)
• CXCR4
• MMP-2

Background: Glycogen synthase kinase-3 beta (GSK3 beta) expression and activity are upregulated in pancreatic cancer tissues. In our previous study, we found that stromal cell-derived factor-1/chemokine receptor C-X-C motif chemokine receptor 4 (SDF-1 alpha/CXCR4) upregulated matrix metalloproteinase 2 (MMP-2) and promoted invasion in PANC1 and SW-1990 pancreatic cancer cells by activating p38 mitogen-activated protein kinase (p38 MAPK). Additionally, inhibition of GSK3 beta reduced MMP-2 secretion. @@@ Methods: To investigate the molecular mechanism of GSK3 beta in pancreatic cancer tissues, we created stable PANC1 cells up-regulation of GSK3 beta by transfecting GSK3 beta overexpression plasmid, and down-regulation of GSK3 beta using two different types of RNA interference. @@@ Results: Western blotting showed that overexpression of GSK3 beta up-regulated CXCR4 and MMP-2 expression; suppression of GSK3 beta down-regulated CXCR4 and MMP-2 protein expression. Up-regulation of MMP2 induced by overexpression of GSK3 beta was blocked by inhibition of CXCR4. Overexpression of GSK3 beta promoted PANC1 cell invasion, and down-regulation of GSK3 beta suppressed PANC1 cell invasion in the transwell invasion assays. However, inhibition of CXCR4 using shRNA attenuated the ability of GSK3 beta to promote PANC1 cell invasion. @@@ Conclusions: This study demonstrated that GSK3 beta promotes PANC1 cell invasion via the CXCR4/MMP-2 pathway.

• 出版日期2015-7-5
• 单位南京医科大学