Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells

Enkhzol Malchinkhuu, Koichi Sato, Yuta Horiuchi, Chihiro Mogi, Susumu Ohwada, Shogo Ishiuchi, Nobuhito Saito, Hitoshi Kurose, Hideaki Tomura, Fumikazu Okajima

研究成果: Contribution to journalArticle査読

71 被引用数 (Scopus)

抄録

A potential role for 1-oleoyl-sn-glycero-3-phosphate or lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in the regulation of malignant diseases has been widely considered. In this study, we found that in transformed astroglial cells, the expression profile of lysophospholipid receptor mRNA and the action modes of LPA and S1P on cell motility were changed: there was a change in the acquisition of the ability of LPA to stimulate cell migration and a change in the migratory response to S1P from stimulation through S1P 1 to inhibition through S1P2. LPA-induced cell migration was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki16425 (3-(4-[4-([1-(2-chlorophenyl)ethoxy] carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfonyl)propanoic acid) or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. The LPA-induced action was also suppressed, although incompletely, by several specific inhibitors for intracellular signaling pathways including Rac1, Cdc42, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase. Nearly complete inhibition of migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Rac1 suppressed JNK but not p38MAPK, while the activity of p38MAPK was abolished by a dominant-negative form of Cdc42. These findings suggest that, in glioma cells, the PI3K/Cdc42/p38MAPK and PI3K/Rac1/JNK pathways are equally important for LPA1 receptor-mediated migration.

本文言語英語
ページ(範囲)6676-6688
ページ数13
ジャーナルOncogene
24
44
DOI
出版ステータス出版済み - 10 6 2005

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 癌研究

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