S1P2 receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN
S1P2 receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN
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DOI：
10.1016/j.bbrc.2007.12.054
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发表时间：
2008-02-22
影响因子：
3.1
通讯作者：
Okajima, Fumikazu
中科院分区：
文献类型：
--
作者：
Malchnkhuu, Enkhzol;Sato, Koichi;Okajima, Fumikazu
磷酸鞘氨醇（SIP）可抑制胶质瘤细胞的迁移。在这里，我们的特点是参与SIP的抑制作用的信号转导机制。在人GNS-3314胶质母细胞瘤细胞中，SIP诱导的细胞迁移抑制与RhoA的激活和Rac 1的抑制相关。S1 P的抑制作用可通过特异于S1 P（2）受体、G α 12或G α 13的羧基端区域、p115 RhoGEF的RGS结构域和RhoA的显性负突变体的小干扰RNA恢复。在U87 MG胶质母细胞瘤和1321 N1星形细胞瘤细胞中也观察到S1 P通过S1 P（2）受体的抑制作用，这些细胞没有10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）的蛋白表达。这些结果表明S1 P（2）受体/G（12/13）-蛋白/Rho信号通路介导了S1 P诱导的胶质瘤细胞迁移抑制。然而，最近被认为是抑制细胞迁移不可或缺的分子的PTEN，可能对胶质瘤细胞中S1 P（2）受体介导的作用并不重要。(c)2007年爱思唯尔公司All rights reserved.
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.