Lysophosphatidic acid induces cell migration through the selective activation of Akt1

Exp Mol Med. 2008 Aug 31;40(4):445-52. doi: 10.3858/emm.2008.40.4.445.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Lysophospholipids / pharmacology*
  • Mice
  • Middle Aged
  • Ovarian Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / physiology
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / agonists*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Substrate Specificity

Substances

  • Lysophospholipids
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • lysophosphatidic acid