S1P(2) receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN.

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 S1P(2) receptor, a carboxyl-terminal region of Galpha12 or Galpha13, an RGS domain of p115RhoGEF, and a dominant-negative mutant of RhoA. The inhibitory action of S1P through S1P(2) 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 S1P(2) receptors/G(12/13)-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 S1P(2) receptor-mediated action in glioma cells.

authors

Malchinkhuu E,Sato K,Maehama T,Mogi C,Tomura H,Ishiuchi S,Yoshimoto Y,Kurose H,Okajima F

doi

10.1016/j.bbrc.2007.12.054

subject

Has Abstract

pub_date

2008-02-22 00:00:00

pages

963-8

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)02680-0

journal_volume

366

pub_type

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