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Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors

文献类型：期刊论文

作者Wang, Yuetong2,3,4,10; Zhang, Jian2,3,4,10; Sun, Dan2,3,4; Huang, Hsin-Yi2,3,4; Wang, Hua2,3,4; Jin, Yujuan2,3,4; Li, Fuming2,3,4; Zheng, Chao2,3,4; Yang, Liu2,3,4; Jiang, Zhonglin2,10
刊名CELL REPORTS
出版日期2019
卷号28期号:2页码:512-+
关键词capacitance sensor biosensor biochip affinity sensor microfluidics cell detection multidimensional data
ISSN号2211-1247
DOI10.1016/j.celrep.2019.06.026
文献子类Article
英文摘要Drug resistance is a significant hindrance to effective cancer treatment. Although resistance mechanisms of epidermal growth factor receptor (EGFR) mutant cancer cells to lethal EGFR tyrosine kinase inhibitors (TKI) treatment have been investigated intensively, how cancer cells orchestrate adaptive response under sublethal drug challenge remains largely unknown. Here, we find that 2-h sublethal TKI treatment elicits a transient drug-tolerant state in EGFR mutant lung cancer cells. Continuous sublethal treatment reinforces this tolerance and eventually establishes long-term TKI resistance. This adaptive process involves H3K9 demethylation-mediated upregulation of branched-chain amino acid aminotransferase 1 (BCAT1) and subsequent metabolic reprogramming, which promotes TKI resistance through attenuating reactive oxygen species (ROS) accumulation. Combination treatment with TKI- and ROS-inducing reagents overcomes this drug resistance in preclinical mouse models. Clinical information analyses support the correlation of BCAT1 expression with the EGFR TKI response. Our findings reveal the importance of BCAT1-engaged metabolism reprogramming in TKI resistance in lung cancer.
学科主题Cell Biology
WOS关键词CANCER PROGRESSION ; BCAT1 PROMOTES ; GROWTH ; EXPRESSION ; PLASTICITY ; CELLS ; ROS
语种英语
WOS记录号WOS:000474580800019
出版者CELL PRESS
版本出版稿
源URL[http://202.127.25.144/handle/331004/1297]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Shanghai 200433, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China;
3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
4.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
5.Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China;
6.Chinese Acad Sci, Inst Hlth Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China;
7.Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China;
8.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA;
9.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China;
10.Univ Chinese Acad Sci, Beijing 100049, Peoples R China,
推荐引用方式
GB/T 7714		 Wang, Yuetong,Zhang, Jian,Sun, Dan,et al. Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors[J]. CELL REPORTS,2019,28(2):512-+.
APA Wang, Yuetong.,Zhang, Jian.,Sun, Dan.,Huang, Hsin-Yi.,Wang, Hua.,...&Ji, Hongbin.(2019).Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors.CELL REPORTS,28(2),512-+.
MLA Wang, Yuetong,et al."Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors".CELL REPORTS 28.2(2019):512-+.

入库方式： OAI收割

来源：上海营养与健康研究所

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