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

页码：445 / 452

页数：8

共 38 条

[1] Akt1/protein kinase Bα is critical for ischemic and VEGF-mediated angiogenesis [J].