Lysophosphatidic acid induces cell migration through the selective activation of Akt1.
10.3858/emm.2008.40.4.445
- Author:
Eun Kyoung KIM
1
;
Sung Ji YUN
;
Kee Hun DO
;
Min Sung KIM
;
Mong CHO
;
Dong Soo SUH
;
Chi Dae KIM
;
Jae Ho KIM
;
Morris J BIRNBAUM
;
Sun Sik BAE
Author Information
1. MRC for Ischemic Tissue Regeneration and Medical Research Institute, School of Medicine, Pusan National University, Busan, Korea. sunsik@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
ascites;
cell movement;
fibroblasts;
lysophosphatidic acid;
1-phosphatidylinositol 3-kinase;
proto-oncogen proteins c-akt
- MeSH:
1-Phosphatidylinositol 3-Kinase/physiology;
Adult;
Aged;
Animals;
Ascites/pathology;
Cell Movement/*drug effects;
Cells, Cultured;
Embryo, Mammalian;
Enzyme Activation/drug effects;
Female;
Humans;
Liver Cirrhosis/pathology;
Lysophospholipids/isolation & purification/*pharmacology;
Mice;
Middle Aged;
Ovarian Neoplasms/pathology;
Pregnancy;
Proto-Oncogene Proteins c-akt/*agonists/*metabolism;
Substrate Specificity
- From:Experimental & Molecular Medicine
2008;40(4):445-452
- CountryRepublic of Korea
- Language:English
-
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.
