Lysophosphatidic acid induces cell migration through the selective activation of Akt1.
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.
Kim
Eun Kyoung
EK
MRC for Ischemic Tissue Regeneration and Medical Research Institute, Department of Internal Medicine, School of Medicine, Pusan National University, Busan 602-739, Korea.
Yun
Sung Ji
SJ
Do
Kee Hun
KH
Kim
Min Sung
MS
Cho
Mong
M
Suh
Dong-Soo
DS
Kim
Chi Dae
CD
Kim
Jae Ho
JH
Birnbaum
Morris J
MJ
Bae
Sun Sik
SS
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
D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C032881:lysophosphatidic acid
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