Re-Configuration of Sphingolipid Metabolism by Oncogenic Transformation

摘要: The sphingolipids are one of the major lipid families in eukaryotes, incorporating a diverse array structural variants that exert powerful influence over cell fate and physiology. Increased expression sphingosine kinase 1 (SPHK1), which catalyses synthesis pro-survival, pro-angiogenic metabolite 1-phosphate (S1P), is well established as hallmark multiple cancers. Metabolic alterations reduce levels pro-apoptotic ceramide, particularly its glucosylation by glucosylceramide synthase (GCS), have frequently been associated with cancer drug resistance. However, simple notion balance between ceramide S1P, often referred to sphingolipid rheostat, dictates survival contrasts recent studies showing highly potent selective SPHK1 inhibitors do not affect proliferation or survival, demonstrating higher some metastatic Recent reports implicated other metabolic enzymes such acid sphingomyelinase (ASM) more strongly pathogenesis, highlight lysosomal metabolism possible weak point for therapeutic targeting cancer. This review describes evidence implicating different their products suggests how newer systems-level approaches may improve our overall understanding oncogenic transformation reconfigures metabolism.