支链氨基酸代谢在肿瘤发生发展中的作用

doi:10.16288/j.yczz.24-095

遗传 ›› 2024, Vol. 46 ›› Issue (6): 438-451.doi: 10.16288/j.yczz.24-095

支链氨基酸代谢在肿瘤发生发展中的作用

沈院(), 李金涛, 尹淼, 雷群英()

复旦大学附属肿瘤医院，肿瘤研究所，上海 200032

收稿日期:2024-04-03 修回日期:2024-05-27 出版日期:2024-06-20 发布日期:2024-05-28
通讯作者:
雷群英，博士，教授，研究方向：营养与肿瘤代谢。E-mail: qlei@fudan.edu.cn; 雷群英，教授，博士生导师，新基石研究员，教育部长江特聘教授，国家杰青获得者，中国细胞生物学学会细胞代谢分会主委、上海市生物化学与分子生物学会副理事长、复旦大学基础医学院院长。获中国青年女科学家奖、上海市自然科学一等奖、谈家桢生命科学创新奖、吴阶平-保罗·杨森医学药学奖等荣誉。以项目负责人主持国家自然科学基金委创新研究群体项目、重大项目、重点项目和科技部国家重点研发项目。研究方向为营养与肿瘤代谢。近年来以胰腺癌为主要模型，揭示了肿瘤高度异质性的代谢内因，提出了胰腺癌的代谢起源假说以及肿瘤早期诊疗的代谢靶向干预新策略，尤其是在支链氨基酸代谢调控肿瘤早期发生领域形成了自己的研究特色；揭示了营养/代谢物及代谢酶可调控细胞表观遗传和翻译后修饰，凸显了代谢物可充当信号分子的兼有功能；发现来自不同碳源的乙酰辅酶A (Ac-CoA)通过表观和乙酰化修饰等多水平调控肿瘤细胞生长。研究成果为肿瘤细胞生长的代谢调控奠定了理论基础，发表在Nature Cell Biology、Nature Metabolism、National Science Review、Cancer Cell、Cell Metabolism、Molecular Cell等学术期刊，并受邀在Nature Cell Biology、Nature Metabolism、Trends in Cell Biology和Journal of Biological Chemistry等杂志发表评述。
作者简介:沈院，博士研究生，专业方向：营养与肿瘤代谢。E-mail: yuanshen20@fudan.edu.cn
基金资助:
国家重点研发计划项目(2020YFA0803402);国家重点研发计划项目(2019YFA0801703);国家自然科学基金项目(82121004);国家自然科学基金项目(82330092);上海市教委创新计划项目(2023ZKZD11);上海市科技重大专项和新基石科学基金资助

The roles of branched-chain amino acids metabolism in tumorigenesis and progression

Yuan Shen(), Jintao Li, Miao Yin, Qunying Lei()

Fudan University Shanghai Cancer Center, Cancer Institutes, Shanghai 200032, China

Received:2024-04-03 Revised:2024-05-27 Published:2024-06-20 Online:2024-05-28
Supported by:
National Key R&D Program of China(2020YFA0803402);National Key R&D Program of China(2019YFA0801703);Natural Science Foundation of China(82121004);Natural Science Foundation of China(82330092);Innovation Program of Shanghai Municipal Education Commission(2023ZKZD11);Shanghai Municipal Science and Technology Major Project, and the New Cornerstone Science Foundation

摘要/Abstract

摘要：

支链氨基酸(branched-chain amino acids，BCAAs)，包括亮氨酸、缬氨酸和异亮氨酸，在调节体内代谢平衡、维持正常生命活动中发挥着重要作用。许多研究报道了它们在肥胖、糖尿病和心血管等疾病中的代谢和功能。近些年研究表明，BCAAs代谢在肿瘤发生发展中也起着重要作用。本文综述了BCAAs代谢在该方面的研究进展，包括与表观遗传调控的关系，特别是围绕肿瘤代谢重塑和代谢感知，讨论了其在肿瘤细胞和肿瘤微环境(tumor microenvironment，TME)中的作用。深入了解BCAAs代谢在肿瘤发生发展中的作用及其机制有助于为开发新的肿瘤治疗策略提供理论基础。

关键词: 支链氨基酸, 肿瘤细胞, 肿瘤微环境, 代谢感知, 代谢重塑, 表观遗传

Abstract:

Branched-chain amino acids (BCAAs), including leucine, valine, and isoleucine, play crucial roles in regulating metabolic balance and maintaining physiological functions in the body. Extensive studies have been focused on their implications in obesity, diabetes, and cardiovascular diseases. Nevertheless, accumulating evidence suggests that BCAAs metabolism also plays significant roles in tumorigenesis and progression. In this review, we overview recent progress of the study on BCAAs metabolism including its relationship with epigenetic regulation. Particularly, we discuss the metabolic reprogramming and metabolic sensing of BCAAs and its intermediate metabolites in tumor cells and microenvironment to decipher their functions. An enhanced understanding of the roles and mechanism of BCAAs metabolism in tumorigenesis and progression will contribute to development of novel therapeutic strategies against tumor.

Key words: BCAAs, tumor cells, tumor microenvironment, metabolic sensing, metabolic reprogramming, epigenetics

沈院, 李金涛, 尹淼, 雷群英. 支链氨基酸代谢在肿瘤发生发展中的作用[J]. 遗传, 2024, 46(6): 438-451.

Yuan Shen, Jintao Li, Miao Yin, Qunying Lei. The roles of branched-chain amino acids metabolism in tumorigenesis and progression[J]. Hereditas(Beijing), 2024, 46(6): 438-451.

图/表 2

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The roles of branched-chain amino acids metabolism in tumorigenesis and progression

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