Cancer treatment strategies targeting sphingolipid metabolism.

摘要: Ceramide and sphingosine-1-phosphate are related sphingolipid metabolites that can be generated through a de novo biosynthetic route or derived from the recycling of membrane sphingomyelin. Both these lipids regulate cellular responses to stress, with generally opposing effects. Sphingosine-1-phosphate functions as growth survival factor, acting ligand for family G protein-coupled receptors, whereas ceramide activates intrinsic extrinsic apoptotic pathways receptor-independent mechanisms. A growing body evidence has implicated ceramide, genes involved in their synthesis, catabolism signaling various aspects oncogenesis, cancer progression drug- radiation resistance. This may explained part by finding both impinge upon PI3K/AKT pathway, which represses apoptosis autophagy. In addition, sphingolipids influence cell cycle progression, telomerase function, migration stem biology. Considering central role mediating physiological well pharmacologically stimulated apoptosis, considered tumor-suppressor lipid. contrast, tumor-promoting lipid, enzyme responsible its synthesis an oncogene. Not surprisingly, genetic mutations result reduced generation, increased reduce steady state levels increase have been identified mechanisms tumor drug resistance cells. Pharmacological tools modulating being developed represent novel therapeutic strategies treatment cancer.