Exp Mol Med.  2008 Aug;40(4):445-452. 10.3858/emm.2008.40.4.445.

Lysophosphatidic acid induces cell migration through the selective activation of Akt1

Affiliations
  • 1MRC for Ischemic Tissue Regeneration and Medical Research Institute, School of Medicine, Pusan National University, Busan, Korea. sunsik@pusan.ac.kr
  • 2Department of Internal Medicine, School of Medicine, Pusan National University, Busan, Korea.
  • 3Department of Obstetrics and Gynecology, School of Medicine, Pusan National University, Busan, Korea.
  • 4University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.

Abstract

Akt plays pivotal roles in many physiological responses including growth, proliferation, survival, metabolism, and migration. In the current studies, we have evaluated the isoform-specific role of akt in lysophosphatidic acid (LPA)-induced cell migration. Ascites from ovarian cancer patients (AOCP) induced mouse embryo fibroblast (MEF) cell migration in a dose-dependent manner. On the other hand, ascites from liver cirrhosis patients (ALCP) did not induce MEF cell migration. AOCP-induced MEF cell migration was completely blocked by pre-treatment of cells with LPA receptor antagonist, Ki16425. Both LPA- and AOCP-induced MEF cell migration was completely attenuated by PI3K inhibitor, LY294002. Furthermore, cells lacking Akt1 displayed defect in LPA-induced cell migration. Re-expression of Akt1 in DKO (Akt1(-/-)Akt2(-/-)) cells restored LPA-induced cell migration, whereas re-expression of Akt2 in DKO cells could not restore the LPA-induced cell migration. Finally, Akt1 was selectively phosphorylated by LPA and AOCP stimulation. These results suggest that LPA is a major factor responsible for AOCP-induced cell migration and signaling specificity of Akt1 may dictate LPA-induced cell migration.

Keyword

ascites; cell movement; fibroblasts; lysophosphatidic acid; 1-phosphatidylinositol 3-kinase; proto-oncogen proteins c-akt

MeSH Terms

1-Phosphatidylinositol 3-Kinase/physiology
Adult
Aged
Animals
Ascites/pathology
Cell Movement/*drug effects
Cells, Cultured
Embryo, Mammalian
Enzyme Activation/drug effects
Female
Humans
Liver Cirrhosis/pathology
Lysophospholipids/isolation & purification/*pharmacology
Mice
Middle Aged
Ovarian Neoplasms/pathology
Pregnancy
Proto-Oncogene Proteins c-akt/*agonists/*metabolism
Substrate Specificity
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