Sphingosine kinase/sphingosine 1-phosphate signaling in cancer therapeutics and drug resistance

Abstract

In this chapter, roles of bioactive sphingolipids, specifically sphingosine kinase 1 (SK1) and 2 (SK2) and their product-sphingosine 1-phosphate (S1P)-will be reviewed with respect to regulation of cancer growth, metastasis, chemotherapeutics, and drug resistance. Sphingolipids are known to be key bioeffector molecules that regulate cancer proliferation, angiogenesis, and cell death. Sphingolipid molecules such as ceramide and S1P have been shown to control cancer cell death and proliferation, respectively. Roles of S1P have been described with respect to their intracellular and extracellular pro-survival and drug resistance functions mostly through S1P receptor (S1PR1-5) engagement. Identification of novel intracellular SK/S1P targets has broadened the existing complex regulatory roles of bioactive sphingolipids in cancer pathogenesis and therapeutics. Thus, deciphering the biochemical and molecular regulation of SK/S1P/S1PR signaling could permit development of novel therapeutic interventions to improve cancer therapy and/or overcome drug resistance. © Springer-Verlag Wien 2013.