title: Lysophosphatidic acid induces cell migration through the selective activation of Akt1.
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.
authors.affiliation: MRC for Ischemic Tissue Regeneration and Medical Research Institute, Department of Internal Medicine, School of Medicine, Pusan National University, Busan 602-739, Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.forename: Kee Hun
authors.initials: KH
authors.lastname: Do
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Mong
authors.initials: M
authors.lastname: Cho
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Suh
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001201:Ascites / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008246:Lysophospholipids / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C032881:lysophosphatidic acid
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