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Pancreatic Cancer Couples Cellular Redox Homeostasis with Non-Canonical Glutamine Metabolism
Wang Yiping1*, Lei Qunying2*
1Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
2The Cancer Metabolism Research Lab,Institutes of Biomedical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
2The Cancer Metabolism Research Lab,Institutes of Biomedical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer， with marginal therapeutic advances in recent years. Targeting the metabolism of pancreatic cancer has emerged as a promising strategy to treat PDAC. Pancreatic cancer cells are highly dependent on glucose and glutamine. Interestingly，pancreatic cancer cells rely on non-canonical glutamine metabolism， but not glucose metabolism， to sustain NADPH production and maintain redox homeostasis. Protein arginine methyltransferase 4 (PRMT4/CARM1) functions as a redox sensor， and couples glutamine metabolism with redox status by modulating arginine methylation of malate dehydrogenase 1 (MDH1).
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