title: GSK3β mediates pancreatic cancer cell invasion in vitro via the CXCR4/MMP-2 Pathway.
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.
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Hepatology, Huai'an Fourth People's Hospital, No.128, Yan an East Road, Qing pu District, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300 People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Feng
keywords: CXCR4; Glycogen synthase kinase-3β (GSK3β); MMP-2