Metabolism of sphingolipids in tumor cells

Abstract

Sphingolipids are a diverse family of complex lipids, in which the determining component is sphingoid base, usually bound to a fatty acid by an amide bond. The metabolism of sphingolipids has long remained on the periphery of biochemical research. Recently, it has begun to attract more and more attention due to the diverse and often multidirectional effects of sphingolipids with a similar chemical structure. Sphingosine and ceramides (N-acylsphingosines), as well as their phosphorylated derivatives (sphingosine-1-phosphate and ceramide-1-phosphates) play the role of signaling molecules. Ceramides can cause apoptosis, regulate the stability of cell membranes and the cellular response to stress. In general, ceramides and sphingoid bases as signaling molecules slow down anabolic and accelerate catabolic reactions, suppressing cell proliferation. Phosphorylated derivatives of ceramide-1-phosphate and sphingosine-1-phosphate, on the contrary, stimulate cell proliferation and division. The significant participation of sphingolipids in the regulation of apoptosis and cell division processes makes them critically important compounds regulating tumor progression. The enzymes of sphingolipid metabolism and the receptors of the corresponding sphingolipids can be considered as targets for antitumor therapy. This review aims to highlight the main pathways of metabolism of sphingolipids in human cells, with special emphasis on the known features of their metabolism in tumor cells.