4.7 Review

Ceramide glycosylation and related enzymes in cancer signaling and therapy

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 139, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111565

Keywords

Ceramide glycosyltransferases; Glycosphingolipids; Cancer risks; Drug resistance; Inhibitors

Funding

  1. Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Guangdong, China [2018B030322011]

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Ceramides, as tumor suppressors, induce apoptotic cell death by acting directly on mitochondria. The balance of ceramide metabolism is regulated by various factors in cancer development. Ceramide metabolic enzymes, especially ceramide glycosyltransferases, play a significant role in regulating tumor progression and are closely associated with the poor prognosis of cancer patients.
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 antitumor 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 regulating 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.

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