The sphingosine kinase-1/sphingosine-1-phosphate axis in cancer: Potential target for anticancer therapy

Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for growth and development of cells. Sphingosine kinase (SPHK) is an important regulator for keeping this balance. It controls the level of S1P and plays important roles in proliferation, migration, and invasion of cancer cells and tumor angiogenesis. There are two isoenzymes of sphingosine kinase, SPHK1 and SPHK2. SPHK1 is ubiquitously expressed in most cancers where it promotes survival and proliferation, while SPHK2 is restricted to only certain tissues and its functions are not well characterized. SPHK1 is currently considered as a novel target for the treatment of cancers. Targeting SPHK1 would provide new strategies for cancer treatment and improve the prognosis of cancer patients. Here we review and summarize the current research findings on the SPHK1-S1P axis in cancer from many aspects including structure, expression, regulation, mechanism, and potential inhibitors.