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

doi:10.1016/j.molcel.2021.07.021

	A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies
	Liu, Zhiwei 1,2; Liu, Yingluo 1,2; Qian, Lili 1; Jiang, Shangwen 1; Gai, Xiameng 3; Ye, Shu 1,4; Chen, Yuehong 1; Wang, Xiaomin 1; Zhai, Linhui 1,3,5; Xu, Jun 1
刊名	MOLECULAR CELL
	2021-10-07
卷号	81 期号:19 页码:4076-+
ISSN号	1097-2765
DOI	10.1016/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.
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关键词	DRUG-SENSITIVITY ; C-RAF ; INHIBITION ; INITIATION ; MUTATIONS ; DISCOVERY ; SELECTION ; STRATEGY ; RECEPTOR ; PATHWAYS
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
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298442]
专题	中国科学院上海药物研究所
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-+.