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
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- 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.
- KMID: 1094124
- DOI: http://doi.org/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.
Keyword
MeSH Terms
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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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