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Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma

文献类型：期刊论文

作者Yang, Zijian1,4; Yan, Cong2,3; Ma, Jiaqiang1,4,5; Peng, Panpan2,3; Ren, Xuelian2,3; Cai, Shangli6; Shen, Xia7; Wu, Yingcheng1,4; Zhang, Shu1,4,7; Wang, Xiaoying1,4
刊名NATURE METABOLISM
出版日期2023-01-02
页码35
DOI10.1038/s42255-022-00710-w
通讯作者Huang, He(hhuang@simm.ac.cn) ; Gao, Qiang(gaoqiang@fudan.edu.cn)
英文摘要Enhanced glycolysis and accumulation of lactate is a common feature in various types of cancer. Intracellular lactate drives a recently described type of posttranslational modification, lysine lactylation (Kla), on core histones. However, the impact of lactylation on biological processes of tumour cells remains largely unknown. Here we show a global lactylome profiling on a prospectively collected hepatitis B virus-related hepatocellular carcinoma (HCC) cohort. Integrative lactylome and proteome analysis of the tumours and adjacent livers identifies 9,275 Kla sites, with 9,256 sites on non-histone proteins, indicating that Kla is a prevalent modification beyond histone proteins and transcriptional regulation. Notably, Kla preferentially affects enzymes involved in metabolic pathways, including the tricarboxylic acid cycle, and carbohydrate, amino acid, fatty acid and nucleotide metabolism. We further verify that lactylation at K28 inhibits the function of adenylate kinase 2, facilitating the proliferation and metastasis of HCC cells. Our study therefore reveals that Kla plays an important role in regulating cellular metabolism and may contribute to HCC progression.
WOS关键词GENE-EXPRESSION ; PROTEIN ; COMPLEX ; CANCER ; CLASSIFICATION ; DEHYDROGENASE ; ACETYLATION ; DISCOVERY ; SOFTWARE ; DATABASE
资助项目National Natural Science Foundation of China[81961128025] ; National Natural Science Foundation of China[81973164] ; National Natural Science Foundation of China[81872321] ; Science and Technology Commission of Shanghai Municipality[19XD1420700] ; Science and Technology Commission of Shanghai Municipality[21JC1401200] ; Science and Technology Commission of Shanghai Municipality[21JC1410100] ; Shanghai Municipal Key Clinical Specialty ; Shanghai Municipal Science and Technology Major Project
WOS研究方向Endocrinology & Metabolism
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000906646700002
源URL[http://119.78.100.183/handle/2S10ELR8/304019]  
专题中国科学院上海药物研究所
通讯作者Huang, He; Gao, Qiang
作者单位1.Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Key Lab Carcinogenesis & Canc Invas,Minist Educ, Shanghai, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, Shanghai, Peoples R China
5.Chinese Acad Sci, Inst Pasteur Shanghai, Ctr Microbes Dev & Hlth, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China
6.Burning Rock Biotech, Med Dept, Guangzhou, Guangdong, Peoples R China
7.Fudan Univ, Jinshan Hosp, Ctr Tumor Diag & Therapy, Shanghai, Peoples R China
8.Fudan Univ, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai, Peoples R China
9.Fudan Univ, State Key Lab Genet Engn, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Zijian,Yan, Cong,Ma, Jiaqiang,et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma[J]. NATURE METABOLISM,2023:35.
APA Yang, Zijian.,Yan, Cong.,Ma, Jiaqiang.,Peng, Panpan.,Ren, Xuelian.,...&Gao, Qiang.(2023).Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.NATURE METABOLISM,35.
MLA Yang, Zijian,et al."Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma".NATURE METABOLISM (2023):35.

入库方式： OAI收割

来源：上海药物研究所

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