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| 1 | Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth显示文摘Epithelial ovarian cancer(EOC) exhibits strong dependency on the tricarboxylic acid(TCA) cycle and oxidative phosphorylation to fuel anabolic process.Here,we show that malate dehydrogenase 2(MDH2),a key enzyme of the TCA cycle,is palmitoylated at cysteine 138(C138) residue,resulting in increased activity of MDH2.We next identify that ZDHHC18 acts as a palmitoyltransferase of MDH2.Glutamine deprivation enhances MDH2 palmitoylation by increasing the binding between ZDHHC18 and MDH2.MDH2 silencing represses mitochondrial respiration as well as ovarian cancer cell proliferation both in vitro and in vivo.Intriguingly,re-expression of wild-type MDH2,but not its palmitoylation-deficient C138 S mutant,sustains mitochondrial respiration and restores the growth as well as clonogenic capability of ovarian cancer cells.Notably,MDH2 palmitoylation level is elevated in clinical cancer samples from patients with high-grade serous ovarian cancer.These observations suggest that MDH2 palmitoylation catalyzed by ZDHHC18 sustains mitochondrial respiration and promotes the malignancy of ovarian cancer,yielding possibilities of targeting ZDHHC18-mediated MDH2 palmitoylation in the treatment of EOC. | Xuan Pei Kai-Yue Li Yuan Shen Jin-Tao Li Ming-Zhu Lei Cai-Yun Fang Hao-Jie Lu Hui-Juan Yang Wenyu Wen Miao Yin Jia Qu Qun-Ying Lei | 2022 | Science China(Life Sciences)2022，65，10： | 1 |
| 2 | Cancer metabolism and dietary interventions显示文摘Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials. | Lin Qian Fan Zhang Miao Yin Qunying Lei | 2022 | Cancer Biology & Medicine2022，19，2： | 0 |
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