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A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies

文献类型：期刊论文

作者Liu, Zhiwei1,2; Liu, Yingluo1,2; Qian, Lili1; Jiang, Shangwen1; Gai, Xiameng3; Ye, Shu1,4; Chen, Yuehong1; Wang, Xiaomin1; Zhai, Linhui1,3,5; Xu, Jun1
刊名MOLECULAR CELL
出版日期2021-10-07
卷号81期号:19页码:4076-+
ISSN号1097-2765
DOI10.1016/j.molcel.2021.07.021
通讯作者Huang, Min(mhuang@simm.ac.cn) ; Tan, Minjia(mjtan@simm.ac.cn)
英文摘要KRAS mutant cancer, characterized by the activation of a plethora of phosphorylation signaling pathways, remains a major challenge for cancer therapy. Despite recent advancements, a comprehensive profile of the proteome and phosphoproteome is lacking. This study provides a proteomic and phosphoproteomic landscape of 43 KRAS mutant cancer cell lines across different tissue origins. By integrating transcriptomics, proteomics, and phosphoproteomics, we identify three subsets with distinct biological, clinical, and therapeutic characteristics. The integrative analysis of phosphoproteome and drug sensitivity information facilitates the identification of a set of drug combinations with therapeutic potentials. Among them, we demonstrate that the combination of DOT1L and SHP2 inhibitors is an effective treatment specific for subset 2 of KRAS mutant cancers, corresponding to a set of TCGA clinical tumors with the poorest prognosis. Together, this study provides a resource to better understand KRAS mutant cancer heterogeneity and identify new therapeutic possibilities.
WOS关键词DRUG-SENSITIVITY ; C-RAF ; INHIBITION ; INITIATION ; MUTATIONS ; DISCOVERY ; SELECTION ; STRATEGY ; RECEPTOR ; PATHWAYS
资助项目Natural Science Foundation of China[81821005] ; Natural Science Foundation of China[91753203] ; Natural Science Foundation of China[81872888] ; Natural Science Foundation of China[91957126] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12000000] ; National Key Science & Technology Program of China[2020YFE0202200] ; National Science & Technology Major Project Key New Drug Creation, Manufacturing Program''[2018ZX09711002-004] ; Science and Technology Commission of Shanghai Municipality[19JC1416300] ; National Basic Research Program of China (973 Program)[2014CBA02004] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMU-ZDCX20181202] ; K.C. Wong Education Foundation
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000706124100004
源URL[http://119.78.100.183/handle/2S10ELR8/298442]  
专题新药研究国家重点实验室
通讯作者Huang, Min; Tan, Minjia
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai, Peoples R China
5.Jiangsu Ocean Univ, Coll Pharm, Jiangsu Key Lab Marine Pharmaceut Compound Screen, Lianyungang, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Dept Bioinformat & Biostat, Shanghai, Peoples R China
7.Beijing Inst Life, Natl Ctr Prot Sci Beijing, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Zhiwei,Liu, Yingluo,Qian, Lili,et al. A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies[J]. MOLECULAR CELL,2021,81(19):4076-+.
APA Liu, Zhiwei.,Liu, Yingluo.,Qian, Lili.,Jiang, Shangwen.,Gai, Xiameng.,...&Tan, Minjia.(2021).A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies.MOLECULAR CELL,81(19),4076-+.
MLA Liu, Zhiwei,et al."A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies".MOLECULAR CELL 81.19(2021):4076-+.

入库方式： OAI收割

来源：上海药物研究所

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