Lysophosphatidic acid induces cell migration through the selective activation of Akt1
Lysophosphatidic acid induces cell migration through the selective activation of Akt1
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DOI：
10.3858/emm.2008.40.4.445
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发表时间：
2008-08-31
影响因子：
12.8
通讯作者：
Bae, Sun Sik
中科院分区：
文献类型：
--
作者：
Kim, Eun Kyoung;Yun, Sung Ji;Bae, Sun Sik
Akt 在许多生理反应中发挥着关键作用，包括生长、增殖、生存、代谢和迁移。在目前的研究中，我们评估了 akt 在溶血磷脂酸 (LPA) 诱导的细胞迁移中的异构体特异性作用。卵巢癌患者（AOCP）的腹水以剂量依赖性方式诱导小鼠胚胎成纤维细胞（MEF）细胞迁移。另一方面，肝硬化患者（ALCP）的腹水不会诱导 MEF 细胞迁移。用 LPA 受体拮抗剂 Ki16425 预处理细胞可完全阻断 AOCP 诱导的 MEF 细胞迁移。 LPA 和 AOCP 诱导的 MEF 细胞迁移均被 PI3K 抑制剂 LY294002 完全减弱。此外，缺乏 Akt1 的细胞在 LPA 诱导的细胞迁移中表现出缺陷。在DKO（Akt1（-/-）Akt2（-/-））细胞中重新表达Akt1可以恢复LPA诱导的细胞迁移，而在DKO细胞中重新表达Akt2不能恢复LPA诱导的细胞迁移。最后，AM 通过 LPA 和 AOCP 刺激选择性磷酸化。这些结果表明 LPA 是 AOCP 诱导的细胞迁移的主要因素，而 Akt1 的信号传导特异性可能决定 LPA 诱导的细胞迁移。
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.