Targeting sphingosine-1-phosphate signaling for cancer therapy  

作　　者：Zuoquan Xie Hong Liu Meiyu Geng 

机构地区：[1]Division of Antitumor Pharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]Division of Chemistry,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Science China(Life Sciences)》2017年第6期585-600,共16页中国科学（生命科学英文版）

基　　金：financial support from the National Natural Science Foundation of China(91229204);the Major Project of the Chinese National Programs for Fundamental Research and Development(2015CB910304)

摘　　要：Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors(S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase(SphK) inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development(particularly in inflammationassociated cancer) as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment.Sphingosine-1-phosphate（S1P） is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors（S1PR1-5） through ＂inside-out signaling＂ or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase（SphK） inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development（particularly in inflammationassociated cancer） as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment.

关 键 词：sphingosine-1-phosphate sphingosine ceramide cancer inflammation immunity 

分 类 号：R730.5[医药卫生—肿瘤]