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Sirtuins 家族在肿瘤发展过程中细胞代谢中的作用。

The roles of sirtuins family in cell metabolism during tumor development.

机构信息

State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing, China; School of life Sciences, Southwest University, Beibei, Chongqing, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing, China; Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing, China.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing, China; Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing, China; Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing, China.

出版信息

Semin Cancer Biol. 2019 Aug;57:59-71. doi: 10.1016/j.semcancer.2018.11.003. Epub 2018 Nov 16.

Abstract

Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD dependent protein modifying enzymes, sirtuins (SIRT1-SIRT7) have multiple catalytic functions such as deacetylase, desuccinylase, demalonylase, demyristoylase, depalmitoylase, and/or mono-ADP-ribosyltransferase. They play important roles in regulating cell metabolism, especially in glucose and lipid metabolism, thereby exerting complex functions in either increasing or decreasing malignant characteristics in tumors. This review highlights the major function and its mechanisms of sirtuins in cellular metabolic reprogramming, such as glucose metabolism including aerobic glycolysis (the Warburg effect), oxidative phosphorylation (OXPHOS)/tricarboxylic acid (TCA) cycle and glutamine metabolism; lipometabolism including fatty acid metabolism, cholesterol metabolism, ketone body metabolism and acetate metabolism; as well as leucine metabolism and the urea cycle in tumorigenesis and cancer development.

摘要

改变能量代谢以满足不受控制的增殖和转移已成为肿瘤的最重要特征之一。然而,其背后的详细分子机制和调节作用尚未完全阐明。作为 NAD 依赖性蛋白修饰酶家族,沉默调节蛋白(SIRT1-SIRT7)具有多种催化功能,如脱乙酰酶、脱琥珀酰酶、脱戊二酰酶、脱豆蔻酰酶、脱棕榈酰酶和/或单 ADP-核糖基转移酶。它们在调节细胞代谢中发挥重要作用,特别是在葡萄糖和脂质代谢中,从而在肿瘤中发挥增加或减少恶性特征的复杂功能。本文重点介绍沉默调节蛋白在细胞代谢重编程中的主要功能及其机制,如葡萄糖代谢包括有氧糖酵解(瓦博格效应)、氧化磷酸化(OXPHOS)/三羧酸(TCA)循环和谷氨酰胺代谢;脂代谢包括脂肪酸代谢、胆固醇代谢、酮体代谢和乙酸盐代谢;以及亮氨酸代谢和尿素循环在肿瘤发生和癌症发展中的作用。

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