S1P2 receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN

Enkhzol Malchinkhuu, Koichi Sato, Tomohiko Maehama, Chihiro Mogi, Hideaki Tomura, Shogo Ishiuchi, Yuhei Yoshimoto, Hitoshi Kurose, Fumikazu Okajima

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Sphingosine 1-phosphate (S1P) induced the inhibition of glioma cell migration. Here, we characterized the signaling mechanisms involved in the inhibitory action by S1P. In human GNS-3314 glioblastoma cells, the S1P-induced inhibition of cell migration was associated with activation of RhoA and suppression of Rac1. The inhibitory action of S1P was recovered by a small interference RNA specific to S1P2 receptor, a carboxyl-terminal region of Gα12 or Gα13, an RGS domain of p115RhoGEF, and a dominant-negative mutant of RhoA. The inhibitory action of S1P through S1P2 receptors was also observed in both U87MG glioblastoma and 1321N1 astrocytoma cells, which have no protein expression of a phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These results suggest that S1P2 receptors/G12/13-proteins/Rho signaling pathways mediate S1P-induced inhibition of glioma cell migration. However, PTEN, recently postulated as an indispensable molecule for the inhibition of cell migration, may not be critical for the S1P2 receptor-mediated action in glioma cells.

Original languageEnglish
Pages (from-to)963-968
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume366
Issue number4
DOIs
Publication statusPublished - Feb 22 2008

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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