The gep proto-oncogene Gα13 mediates lysophosphatidic acid-mediated migration of pancreatic cancer cells

Pancreas. 2013 Jul;42(5):819-28. doi: 10.1097/MPA.0b013e318279c577.

Abstract

Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoblotting
  • Lysophospholipids / pharmacology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Protein Binding / genetics
  • Proto-Oncogene Mas
  • RNA Interference
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Lysophospholipids
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Receptors, Lysophosphatidic Acid
  • GTP-Binding Protein alpha Subunits, G12-G13
  • lysophosphatidic acid