Ceramide and sphingosine-1-phosphate in cancer, two faces of the sphinx

It is now well appreciated that bioactive sphingolipids represent an important family of structural and signaling lipids. The focus on sphingolipid research has grown exponentially since their bioactive properties were first described just over two decades ago. Today, sphingolipid metabolites are established regulators of myriad cellular and pathological processes. Sphingolipid research is intricate due to the role of these molecules in vastly different biologies, their distinct structural properties and interconnected metabolic pathways. Ceramide and sphingosine-1-phosphate (S1P) have been defined as reciprocal regulators of cellular fate, and not surprisingly have been targeted for their role in cancer and their therapeutic potential. This review will describe the specific ways the sphingolipid metabolic enzymes and lipids are metabolically interconnected and highlight recent findings to support the reciprocal role of ceramide and S1P in cellular processes and in cancer.