Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way, Oakland, CA 94609, USA.
Biochimie. 2010 Jun;92(6):716-23. doi: 10.1016/j.biochi.2010.02.014. Epub 2010 Feb 16.
Nearly two decades ago, the sphingolipid metabolite sphingosine 1-phosphate was discovered to function as a lipid mediator and regulator of cell proliferation. Since that time, sphingosine 1-phosphate has been shown to mediate a diverse array of fundamental biological processes including cell proliferation, migration, invasion, angiogenesis, vascular maturation and lymphocyte trafficking. Sphingosine 1-phosphate acts primarily via signaling through five ubiquitously expressed G protein-coupled receptors. Intracellular sphingosine 1-phosphate molecules are transported extracellularly and gain access to cognate receptors for autocrine and paracrine signaling and for signaling at distant sites reached through blood and lymphatic circulation systems. Intracellular pools of sphingosine 1-phosphate available for signaling are tightly regulated primarily by three enzymes: sphinosine kinase, S1P lyase and S1P phosphatase. Alterations in sphingosine 1-phosphate as well as the enzymes involved in its synthesis and catabolism have been observed in many types of malignancy. These enzymes are being evaluated for their role in mediating cancer formation and progression, as well as their potential to serve as targets of anti-cancer therapeutics. In this review, the impact of sphingosine 1-phosphate, its cognate receptors, and the enzymes of sphingosine 1-phosphate metabolism on cell survival, apoptosis, autophagy, cellular transformation, invasion, angiogenesis and hypoxia in relation to cancer biology and treatment are discussed.
近二十年前，鞘氨醇 1-磷酸（Sphingosine 1-phosphate）这种鞘脂代谢物被发现具有作为脂质介质和细胞增殖调节剂的功能。自那时以来，已表明鞘氨醇 1-磷酸可介导包括细胞增殖、迁移、侵袭、血管生成、血管成熟和淋巴细胞运输在内的各种基本生物学过程。鞘氨醇 1-磷酸主要通过五种广泛表达的 G 蛋白偶联受体信号传导发挥作用。细胞内的鞘氨醇 1-磷酸分子被运送到细胞外，并与同源受体结合，用于自分泌和旁分泌信号以及通过血液和淋巴循环系统到达远处部位的信号。可用于信号传导的细胞内鞘氨醇 1-磷酸池主要受三种酶的严格调控：鞘氨醇激酶、S1P 裂合酶和 S1P 磷酸酶。在许多类型的恶性肿瘤中都观察到鞘氨醇 1-磷酸及其合成和分解代谢中涉及的酶的改变。这些酶正在评估它们在介导癌症形成和进展中的作用，以及它们作为抗癌治疗靶点的潜力。在这篇综述中，讨论了鞘氨醇 1-磷酸、其同源受体以及鞘氨醇 1-磷酸代谢酶对与癌症生物学和治疗相关的细胞存活、细胞凋亡、自噬、细胞转化、侵袭、血管生成和缺氧的影响。
