气候变化领域集成服务门户(CCPortal): Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs

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DOI	10.1073/pnas.2018229118
	Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs
	Saavedra-García P.; Roman-Trufero M.; Al-Sadah H.A.; Blighe K.; López-Jiménez E.; Christoforou M.; Penfold L.; Capece D.; Xiong X.; Miao Y.; Parzych K.; Caputo V.S.; Siskos A.P.; Encheva V.; Liu Z.; Thiel D.; Kaiser M.F.; Piazza P.; Chaidos A.; Karadimitris A.; Franzoso G.; Snijders A.P.; Keun H.C.; Oyarzún D.A.; Barahona M.; Auner H.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Cancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome. Cellular recovery from proteasome inhibition involved protracted and dynamic changes of glucose and lipid metabolism and suppression of mitochondrial function. We demonstrate that recovering cells are more vulnerable to specific insults than acutely stressed cells and identify the general control nonderepressable 2 (GCN2)-driven cellular response to amino acid scarcity as a key recovery-associated vulnerability. Using a transcriptome analysis pipeline, we further show that GCN2 is also a stress-independent bona fide target in transcriptional signature-defined subsets of solid cancers that share molecular characteristics. Thus, identifying cellular trade-offs tied to the resolution of chemotherapy-induced stress in tumor cells may reveal new therapeutic targets and routes for cancer therapy optimization. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	GCN2; Metabolism; Myeloma; Proteasome; Proteostasis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179748
作者单位	Cancer Cell Protein Metabolism, Department of Immunology and Inflammation, Imperial College London, London, W12 0NN, United Kingdom; The Hugh and Josseline Langmuir Centre for Myeloma Research, Imperial College London, London, W12 0NN, United Kingdom; Clinical Bioinformatics Research, London, W1B 3HH, United Kingdom; Cellular Stress, MRC London Institute of Medical Sciences, London, W12 0NN, United Kingdom; Centre for Molecular Immunology and Inflammation, Department of Immunology and Inflammation, Imperial College London, London, W12 0NN, United Kingdom; Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom; Proteomics Platform, The Francis Crick Institute, London, NW1 1AT, United Kingdom; Department of Mathematics, Imperial College London, London, SW7 2AZ, United Kingdom; Department of Brain Sciences, Imperial College London, London, W12 0NN, United Kingdom; UK Dementia Research Institute, Imperial College, London, W12 0NN, United Kingdom; Myeloma Molecular Therapy, ...
推荐引用方式 GB/T 7714	Saavedra-García P.,Roman-Trufero M.,Al-Sadah H.A.,et al. Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs[J],2021,118(17).
APA	Saavedra-García P..,Roman-Trufero M..,Al-Sadah H.A..,Blighe K..,López-Jiménez E..,...&Auner H.W..(2021).Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Saavedra-García P.,et al."Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).