S1P(2) receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN.
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.
Malchinkhuu
Enkhzol
E
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Sato
Koichi
K
Maehama
Tomohiko
T
Mogi
Chihiro
C
Tomura
Hideaki
H
Ishiuchi
Shogo
S
Yoshimoto
Yuhei
Y
Kurose
Hitoshi
H
Okajima
Fumikazu
F
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D013110:Sphingosine; C032881:lysophosphatidic acid