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|Title:||O-GlcNAcylation of fatty acid synthase under nutritional stress as a pro-survival mechanism in cancer cells||Authors:||WONG YIN KWAN||Keywords:||Proteomics, O-GlcNAc, Cancer, Metabolism, LC-MS/MS||Issue Date:||28-Jun-2021||Citation:||WONG YIN KWAN (2021-06-28). O-GlcNAcylation of fatty acid synthase under nutritional stress as a pro-survival mechanism in cancer cells. ScholarBank@NUS Repository.||Abstract:||Protein O-GlcNAcylation is a specific form of protein glycosylation that targets a wide range of proteins with important functions. O-GlcNAcylation is known to be deregulated in cancer and has been linked to multiple aspects of cancer pathology. Despite its ubiquity and importance, the current understanding of the role of O-GlcNAcylation in the stress response remains limited. In this study, we performed a quantitative chemical proteomics-based open study of the O-GlcNAcome in HeLa cells, and identified 163 differentially-glycosylated proteins under starvation, involving multiple metabolic pathways. Among them, fatty acid metabolism was found to be targeted and subsequent analysis confirmed that fatty acid synthase (FASN) is O-GlcNAcylated. O-GlcNAcylation led to enhanced de novo fatty acid synthesis activity, and fatty acids contributed to the cytoprotective effects of O-GlcNAcylation under starvation. Moreover, dual inhibition of O-GlcNAcylation and FASN displayed a strong synergistic effect in vitro in inducing cell death in cancer cells. Together, the results from this study provide novel insights into the role of O-GlcNAcylation in the nutritional stress response and suggest the potential of combining inhibition of O-GlcNAcylation and fatty acid synthesis in cancer therapy.||URI:||https://scholarbank.nus.edu.sg/handle/10635/214501|
|Appears in Collections:||Ph.D Theses (Open)|
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