The first reaction of ceramide glycosylation in sphingolipid metabolism is catalyzed by glucosylceramide synthase (GCS), which changes ceramide into glucosylceramide. By regulating ceramide and glycosphingolipids (GSLs), this glycosylation by GCS is a crucial step in controlling the modulation of cellular activities. Ceramide levels rise in response to stresses like chemotherapy, which causes cells to enter apoptosis or autophagy. Ceramide glycosylation, however, quickly removes ceramide and, as a result, these induced processes, protecting cancer cells.Additionally, persistently increased ceramide glycosylation can raise GSLs and contribute to the selection of drug-resistant cancer cells. In numerous drug-resistant cancer cells as well as breast, colon, and leukemia tumors that exhibit a poor response to chemotherapy, GCS is overexpressed. Inhibition of GCS makes cancer cells more susceptible to anticancer medications and kills cancer stem cells because ceramide glycosylation by GCS is a rate-limiting step in GSL synthesis.
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