期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 366, 期 4, 页码 963-968出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.12.054
关键词
glioma; cell migration; sphingosine-1-phosphate; lysophosphatidic acid; PTEN
Sphingosine I-phosphate (SIP) induced the inhibition of glioma cell migration. Here, we characterized the signaling mechanisms involved in the inhibitory action by SIP. In human GNS-3314 glioblastoma cells, the SIP-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 G alpha 12 or G alpha 13, 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. (c) 2007 Elsevier Inc. All rights reserved.
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