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Digestive Diseases and Sciences

, Volume 58, Issue 12, pp 3524–3533 | Cite as

Lysophosphatidic Acid Stimulates Activation of Focal Adhesion Kinase and Paxillin and Promotes Cell Motility, via LPA1–3, in Human Pancreatic Cancer

  • Yan Liao
  • Ganggang Mu
  • Lingli Zhang
  • Wei Zhou
  • Jun Zhang
  • Honggang Yu
Original Article

Abstract

Background

Pancreatic cancer is highly metastatic and with poor prognosis. In previous studies, lysophosphatidic acid (LPA) was shown to be a critical component of ascites which promoted the invasion and metastasis of pancreatic cancer. Two focal adhesion proteins, focal adhesion kinase (FAK) and paxillin, were crucially involved in cell migration, cytoskeleton reorganization, and the dynamics of focal adhesion.

Objectives

This study examined the involvement of LPA1–3 in LPA-induced activation of FAK and paxillin, and in cell motility, in pancreatic cancer PANC-1 cells.

Methods

Reverse transcriptase polymerase chain reaction analysis was used to examine mRNA expression of LPA receptors in PANC-1. Cellular protein expression of FAK and paxillin was analyzed by western blotting. The subcellular location of FAK and paxillin was visualized by immunofluorescence. Cell migration was measured by use of a transwell migration chamber.

Results

Three LPA receptors (LPA1, LPA2, and LPA3) were significantly expressed in PANC-1 cells. Treatment with LPA induced both time and dose-dependent tyrosine phosphorylation of FAK and paxillin. LPA also affected translocation of FAK and paxillin from cytoplasm to focal adhesions at the cell periphery and enhanced cell motility of PANC-1. Pretreatment with 3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl)benzylsulfanyl)propanoic acid (Ki16425), an antagonist of LPA1 and LPA3, before LPA attenuated the LPA-induced tyrosine phosphorylation and redistribution of FAK and paxillin and abrogated LPA-induced cellular migration activity.

Conclusions

These results suggest LPA induces activation of FAK and paxillin via LPA1–3, which may contribute to the increased cell motility in human pancreatic cancer PANC-1 cells. Thus, an understanding of the regulation by LPA of cell motility in pancreatic cancer could identify novel targets for therapy.

Keywords

Lysophosphatidic acid LPA receptor Focal adhesion kinase Paxillin Pancreatic cancer Cell migration 

Notes

Acknowledgments

We sincerely thank Hong Xia (Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, China) for his administrative support in this work. This work was supported by the National Natural Science Foundation of China (no. 81172350) and the Fundamental Research Funds for the Chinese Central Universities (no. 201130202020016 and no. 2012302020214).

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yan Liao
    • 1
  • Ganggang Mu
    • 1
  • Lingli Zhang
    • 1
  • Wei Zhou
    • 1
  • Jun Zhang
    • 1
  • Honggang Yu
    • 1
  1. 1.Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina

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