Department of Pharmacology, University Medicine Greifswald, 17487 Greifswald, Germany.
Clinic of Neurosurgery, University Medicine Greifswald, 17487 Greifswald, Germany.
Int J Mol Sci. 2017 Nov 17;18(11):2448. doi: 10.3390/ijms18112448.
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
多功能鞘氨醇-1-磷酸（S1P）是一种脂质信号分子，也是几种癌症类型发展过程中的中央调节剂。近年来，有关 S1P 在多形性胶质母细胞瘤（GBM）进展中的作用的有趣信息越来越多，GBM 是成人中最具侵袭性和最常见的脑肿瘤。S1P 调节 GBM 中的许多细胞过程，如肿瘤发生、增殖和存活、侵袭、迁移、转移和干细胞行为。这些过程受五种 G 蛋白偶联 S1P 受体（S1PR1-5）家族调节，可能涉及主要未知的细胞内靶点。每种 S1PR 亚型的不同表达模式和多种细胞内信号通路使 S1P 能够发挥其多效性的细胞作用。几项研究表明 S1P 水平的改变、S1PRs 和 S1P 代谢酶在 GBM 病理生理学中的参与。虽然 S1P 的致癌作用涉及几种激酶和转录因子的激活，但在 GBM 中，与特定 G 蛋白（Gi、Gq 和 G12/13）偶联的信号通路和下游介导的效应仍有待详细阐明。这篇综述总结了最近关于 S1P 及其受体在 GBM 中的作用的研究结果。我们进一步强调了目前对被认为对调节 GMB 中细胞过程和最终患者预后至关重要的信号通路的深入了解。
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