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KMID : 0620920080400040445
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Experimental & Molecular Medicine
2008 Volume.40 No. 4 p.445 ~ p.452
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Lysophosphatidic acid induces cell migration through the selective activation of Akt1
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Kim Eun-Kyung
Cho Mong
Kim Chi-Dae
Yun Sung-Ji
Suh Dong-Soo
Kim Jae-Ho
Do Ki-Hun
Kim Min-Sung
Birnbaum Morris J.
Bae Sun-Sik
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Abstract
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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.
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KEYWORD
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ascites, cell movement, fibroblasts, lysophosphatidic acid, 1-phosphatidylinositol 3-kinase, proto-oncogen proteins c-akt
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