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Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer

文献类型：期刊论文

作者Jin, Nan1,2; Bi, Aiwei1,2; Lan, Xiaojing1; Xu, Jun1,2; Wang, Xiaomin1,2; Liu, Yingluo1,2; Wang, Ting1,2; Tang, Shuai1; Zeng, Hanlin1,2; Chen, Ziqi1,2
刊名NATURE COMMUNICATIONS
出版日期2019-06-20
卷号10页码:15
ISSN号2041-1723
DOI10.1038/s41467-019-10427-2
通讯作者Geng, Meiyu(mygeng@simm.ac.cn) ; Lin, Shu-Hai(shuhai@xmu.edu.cn) ; Huang, Min(mhuang@simm.ac.cn)
英文摘要One of the biggest hurdles for the development of metabolism-targeted therapies is to identify the responsive tumor subsets. However, the metabolic vulnerabilities for most human cancers remain unclear. Establishing the link between metabolic signatures and the oncogenic alterations of receptor tyrosine kinases (RTK), the most well-defined cancer genotypes, may precisely direct metabolic intervention to a broad patient population. By integrating metabolomics and transcriptomics, we herein show that oncogenic RTK activation causes distinct metabolic preference. Specifically, EGFR activation branches glycolysis to the serine synthesis for nucleotide biosynthesis and redox homeostasis, whereas FGFR activation recycles lactate to fuel oxidative phosphorylation for energy generation. Genetic alterations of EGFR and FGFR stratify the responsive tumors to pharmacological inhibitors that target serine synthesis and lactate fluxes, respectively. Together, this study provides the molecular link between cancer genotypes and metabolic dependency, providing basis for patient stratification in metabolism-targeted therapies.
WOS关键词GROWTH-FACTOR ; THERAPEUTIC RESPONSE ; LUNG ADENOCARCINOMAS ; SERINE BIOSYNTHESIS ; CELL-LINES ; IN-VITRO ; INHIBITOR ; RESISTANCE ; PROMOTES ; DEHYDROGENASE
资助项目China International Science and Technology Cooperation Program[2015DFM30040] ; National Key Research and Development Program of China[2016YFC0904800] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[81672911] ; National Natural Science Foundation of China[81573464] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12000000] ; K.C. Wong Education Foundation
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000472139900004
源URL[http://119.78.100.183/handle/2S10ELR8/289557]  
专题新药研究国家重点实验室
通讯作者Geng, Meiyu; Lin, Shu-Hai; Huang, Min
作者单位1.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Chem Prote Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
5.Agilent Technol China Co Ltd, 1350 North Sichuan Rd, Shanghai 200080, Peoples R China
6.Macau Univ Sci & Technol, Macau Inst Appl Res Med & Hlth, State Key Lab Qual Res Chinese Med, Ave Wai Long, Taipa 999078, Macao, Peoples R China
7.Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Sch Life Sci, 4221 South Xiangan Rd, Xiamen 361102, Fujian, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Nan,Bi, Aiwei,Lan, Xiaojing,et al. Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer[J]. NATURE COMMUNICATIONS,2019,10:15.
APA Jin, Nan.,Bi, Aiwei.,Lan, Xiaojing.,Xu, Jun.,Wang, Xiaomin.,...&Huang, Min.(2019).Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer.NATURE COMMUNICATIONS,10,15.
MLA Jin, Nan,et al."Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer".NATURE COMMUNICATIONS 10(2019):15.

入库方式： OAI收割

来源：上海药物研究所

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