title: The gep proto-oncogene Gα13 mediates lysophosphatidic acid-mediated migration of pancreatic cancer cells.
abstract: OBJECTIVE
  Tumor microenvironment, defined by a variety of growth factors including lysophosphatidic acid (LPA), whose levels are increased in pancreatic cancer patients, plays a major role in the genesis and progression of pancreatic cancer. Because the gep proto-oncogenes, Gα12 and Gα13, are implicated in LPA-stimulated oncogenic signaling, this study is focused on evaluating the role of these proto-oncogenes in LPA-stimulated invasive migration of pancreatic cancer cells.
  
  
  METHODS
  Effect of LPA on the migration and proliferation of pancreatic cancer cells was assessed using BxPC3, Dan-G, MDAPanc-28, Panc-1, and PaCa-2 cell lines. The role of Gα13 in the migration of pancreatic cancer cells was interrogated by disrupting lysophosphatidic acid receptor-Gα13 interaction using CT13, a dominant negative mutant of Gα13, and by silencing the expression of Gα13.
  
  
  RESULTS
  Results indicate that LPA stimulates the migration of pancreatic cancer cells and such LPA-stimulated migratory response is mediated by Gα13. Furthermore, the results establish that the silencing of Gα13, but not Gα12, abrogates LPA-stimulated invasive migration of pancreatic cancer cells.
  
  
  CONCLUSIONS
  These results report for the first time a critical role for Gα13 in LPA-stimulated invasive migration of pancreatic cancer cells. These findings identify LPA-lysophosphatidic acid receptor-Gα13 signaling node as a novel therapeutic target for pancreatic cancer treatment and control.
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Gardner
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Ha
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Jayaraman
authors.forename: Danny N
authors.initials: DN
authors.lastname: Dhanasekaran
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D008246:Lysophospholipids / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008246:Lysophospholipids; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D049368:Receptors, Lysophosphatidic Acid; D044365:GTP-Binding Protein alpha Subunits, G12-G13; C032881:lysophosphatidic acid