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.
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 humanpancreatic cancer PANC-1 cells. Thus, an understanding of the regulation by LPA of cell motility in pancreatic cancer could identify novel targets for therapy.
Authors: Byungdo B Han; Suyang Li; Meng Tong; Andrew S Holpuch; Richard Spinney; Daren Wang; Michael B Border; Zhongfa Liu; Sachin Sarode; Ping Pei; Steven P Schwendeman; Susan R Mallery Journal: Cancer Prev Res (Phila) Date: 2015-02-24
Authors: Mingyang Liu; Jingxuan Yang; Yuqing Zhang; Zhijun Zhou; Xiaobo Cui; Liyang Zhang; Kar-Ming Fung; Wei Zheng; Felicia D Allard; Eric U Yee; Kai Ding; Huanwen Wu; Zhiyong Liang; Lei Zheng; Martin E Fernandez-Zapico; Yi-Ping Li; Michael S Bronze; Katherine T Morris; Russell G Postier; Courtney W Houchen; Jing Yang; Min Li Journal: Clin Cancer Res Date: 2018-04-03 Impact factor: 12.531