Abstract
BackgroundGlycogen synthase kinase-3β (GSK3β) 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-1α/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 GSK3β reduced MMP-2 secretion.MethodsTo investigate the molecular mechanism of GSK3β in pancreatic cancer tissues, we created stable PANC1 cells up-regulation of GSK3β by transfecting GSK3β overexpression plasmid, and down-regulation of GSK3β using two different types of RNA interference.ResultsWestern blotting showed that overexpression of GSK3β up-regulated CXCR4 and MMP-2 expression; suppression of GSK3β down-regulated CXCR4 and MMP-2 protein expression. Up-regulation of MMP2 induced by overexpression of GSK3β was blocked by inhibition of CXCR4. Overexpression of GSK3β promoted PANC1 cell invasion, and down-regulation of GSK3β suppressed PANC1 cell invasion in the transwell invasion assays. However, inhibition of CXCR4 using shRNA attenuated the ability of GSK3β to promote PANC1 cell invasion.ConclusionsThis study demonstrated that GSK3β promotes PANC1 cell invasion via the CXCR4/MMP-2 pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0216-y) contains supplementary material, which is available to authorized users.
Highlights
Glycogen synthase kinase-3β (GSK3β) expression and activity are upregulated in pancreatic cancer tissues
Overexpression of GSK3β upregulates Chemokine receptor C-X-C motif chemokine receptor 4 (CXCR4) and matrix metalloproteinase 2 (MMP-2) To elucidate the effect of GSK3β on the expression of CXCR4 and MMP-2 in pancreatic cancer cells, we overexpresses GSK3β in PANC1 and SW-1990 cells
We determine the expression of CXCR4 and MMP2 in PANC1 cells overexpressing GSK3β using Western blotting
Summary
Glycogen synthase kinase-3β (GSK3β) expression and activity are upregulated in pancreatic cancer tissues. Further studies are needed to identify novel molecular therapeutic targets which determine the sensitivity of pancreatic cells to chemotherapeutic agents and ionizing radiation [1]. Recent studies suggested that GSK3β can promote the invasion of pancreatic, lung, breast and liver cancer cells, and inhibition of GSK3β induces apoptosis [8,9,10]. These results have led researchers to propose GSK3β as a potential therapeutic target in cancer. Recent studies have indicated that GSK3β promotes the proliferation and invasion of pancreatic cancer cells. Inhibition of GSK3β triggered an apoptotic response in pancreatic cancer cells via a JNK-dependent mechanism [11], and attenuated cell survival and proliferation and induced apoptosis in pancreatic cancer cell lines [5]
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