Ceramide glycosylation and related enzymes in cancer signaling and therapy.

Abstract Ceramides, the core of the sphingolipid metabolism, draw wide attention as tumor suppressor, and act directly on mitochondria to trigger apoptotic cell death. Ceramide-based therapies are being developed by using promote ceramide generating agents. The ceramide metabolism balance is regulated by multifaceted factors in cancer development. Ceramide metabolic enzymes can increase the elimination of ceramide and counteract the anti-tumor effects of ceramide. However, recent research showed that these metabolic enzymes were highly expressed in several cancers. Especially ceramide glycosyltransferases, they catalyze ceramide glycosylation and synthesis the skeleton of glycosphingolipids (GSLs), play an important role in regulatin g tumor progression and have a significant correlation with the poor prognosis of cancer patients. To further understand the biological characteristics of ceramide metabolism in tumor, this review focuses on the role of ceramide glycosylation and related enzymes in cancer signaling and therapy. Besides, the research on multidrug resistance and potential inhibitors of ceramide glycosyltransferases are also discussed. Advance study on the structure of ceramide glycosyltransferases and ceramide glycosylation signaling pathway will open the path to new therapies and treatments.