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

Jacob A. Gardner, Ji Hee Ha, Muralidharan Jayaraman, Danny N. Dhanasekaran

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)819-828
Number of pages10
JournalPancreas
Volume42
Issue number5
DOIs
StatePublished - Jul 2013

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Fingerprint Dive into the research topics of 'The gep proto-oncogene Gα<sub>13</sub> mediates lysophosphatidic acid-mediated migration of pancreatic cancer cells'. Together they form a unique fingerprint.

Cite this