Lysophosphatidic acid induces cell migration through the selective activation of Akt1

被引：38
作者：
Kim, Eun Kyoung [1 ,2 ]
Yun, Sung Ji [1 ,2 ]
Do, Kee Hun [1 ,2 ]
Kim, Min Sung [1 ,2 ]
Cho, Mong [3 ]
Suh, Dong-Soo [4 ]
Kim, Chi Dae [1 ,2 ]
Kim, Jae Ho [1 ,2 ]
Birnbaum, Morris J. [5 ]
Bae, Sun Sik [1 ,2 ]
机构：
[1] Pusan Natl Univ, MRC Ischem Tissue Regenerat, Pusan 602739, South Korea
[2] Pusan Natl Univ, Med Res Inst, Pusan 602739, South Korea
[3] Pusan Natl Univ, Dept Internal Med, Pusan 602739, South Korea
[4] Pusan Natl Univ, Dept Obstet & Gynecol, Sch Med, Pusan 602739, South Korea
[5] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
来源：
EXPERIMENTAL AND MOLECULAR MEDICINE | 2008年 / 40卷 / 04期
关键词：
ascites; cell movement; fibroblasts; lysophosphatidic acid; 1-phosphatidylinositol; 3-kinase; proto-oncogen proteins c-akt;
D O I：
10.3858/emm.2008.40.4.445
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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, AM 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.
引用
收藏
页码：445 / 452
页数：8
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