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: Enkhzol Malchinkhuu, Koichi Sato, Tomohiko Maehama, Chihiro Mogi, Hideaki Tomura, Shogo Ishiuchi, Yuhei Yoshimoto, Hitoshi Kurose, Fumikazu Okajima
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 366 Issue 4 Pg. 963-8 (Feb 22 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18088600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lysophospholipids
• Receptors, Lysosphingolipid
• sphingosine 1-phosphate
• PTEN Phosphohydrolase
• PTEN protein, human
• GTP-Binding Protein alpha Subunits, G12-G13
• rac1 GTP-Binding Protein
• rhoA GTP-Binding Protein
• Sphingosine
• lysophosphatidic acid

Topics

• Cell Line, Tumor
• Cell Movement (drug effects)
• GTP-Binding Protein alpha Subunits, G12-G13
• Glioma (enzymology, pathology)
• Humans
• Lysophospholipids (pharmacology)
• PTEN Phosphohydrolase (metabolism)
• Receptors, Lysosphingolipid (metabolism)
• Signal Transduction (drug effects)
• Sphingosine (analogs & derivatives, pharmacology)
• rac1 GTP-Binding Protein (metabolism)
• rhoA GTP-Binding Protein (metabolism)