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Cancer Cell International
Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

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

Authors: Xu Ying, Li Jing, Shijie Ma, Qianjun Li, Xiaoling Luo, Zhenguo Pan, Yanling Feng, Pan Feng

Published in: Cancer Cell International | Issue 1/2015

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Abstract

Background

Glycogen 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.

Methods

To 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.

Results

Western 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.

Conclusions

This study demonstrated that GSK3β promotes PANC1 cell invasion via the CXCR4/MMP-2 pathway.
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Metadata
Title
GSK3β mediates pancreatic cancer cell invasion in vitro via the CXCR4/MMP-2 Pathway
Authors
Xu Ying
Li Jing
Shijie Ma
Qianjun Li
Xiaoling Luo
Zhenguo Pan
Yanling Feng
Pan Feng
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0216-y

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