Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma

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Abstract

Ceramide synthase 1 (CERS1) is the most highly expressed CERS in the central nervous system, and ceramide with an 18-carbon-containing fatty acid chain (C18- ceramide) in the brain plays important roles in signaling and sphingolipid development. However, the roles of CERS1 and C18-ceramide in glioma are largely unknown. In the present study, measured by electrospray ionization linear ion trap mass spectrometry, C18-ceramide was significantly lower in glioma tumor tissues compared with controls (P < 0.001), indicating that C18-ceramide might have a role in glioma. These roles were examined by reconstitution of C18-ceramide in U251 and A172 glioma cells via addition of exogenous C18-ceramide or overexpression of CERS1, which has been shown to specifically induce the generation of C18-ceramide. Overexpression of CERS1 or adding exogenous C18-ceramide inhibited cell viability and induced cell death by activating endoplasmic reticulum stress, which induced lethal autophagy and inhibited PI3K/AKT signal pathway in U251 and A172 glioma cells. Moreover, overexpression of CERS1 or adding exogenous C18-ceramide increased the sensitivity of U251 and A172 glioma cells to teniposide (VM-26). Thus, the combined therapy of CERS1/ C18-ceramide and VM-26 may be a novel therapeutic strategy for the treatment of human glioma.

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Wang, Z., Wen, L., Zhu, F., Wang, Y., Xie, Q., Chen, Z., & Li, Y. (2017). Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma. Oncotarget, 8(61), 104022–104036. https://doi.org/10.18632/oncotarget.21955

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