气候变化领域集成服务门户(CCPortal): MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer

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DOI	10.1126/science.aau8768
	MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer
	Cipponi A.; Goode D.L.; Bedo J.; McCabe M.J.; Pajic M.; Croucher D.R.; Rajal A.G.; Junankar S.R.; Saunders D.N.; Lobachevsky P.; Papenfuss A.T.; Nessem D.; Nobis M.; Warren S.C.; Timpson P.; Cowley M.; Vargas A.C.; Qiu M.R.; Generali D.G.; Keerthikumar S.; Nguyen U.; Corcoran N.M.; Long G.V.; Blay J.-Y.; Thomas D.M.
发表日期	2020
ISSN	10959203
起始页码	1127
结束页码	1131
卷号	368 期号:6495
英文摘要	In microorganisms, evolutionarily conserved mechanisms facilitate adaptation to harsh conditions through stress-induced mutagenesis (SIM). Analogous processes may underpin progression and therapeutic failure in human cancer. We describe SIM in multiple in vitro and in vivo models of human cancers under nongenotoxic drug selection, paradoxically enhancing adaptation at a competing intrinsic fitness cost. A genome-wide approach identified the mechanistic target of rapamycin (MTOR) as a stress-sensing rheostat mediating SIM across multiple cancer types and conditions. These observations are consistent with a two-phase model for drug resistance, in which an initially rapid expansion of genetic diversity is counterbalanced by an intrinsic fitness penalty, subsequently normalizing to complete adaptation under the new conditions. This model suggests synthetic lethal strategies to minimize resistance to anticancer therapy. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
语种	英语
来源机构	Science (New York, N.Y.)
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133446
推荐引用方式 GB/T 7714	Cipponi A.,Goode D.L.,Bedo J.,et al. MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer[J]. Science (New York, N.Y.),2020,368(6495).
APA	Cipponi A..,Goode D.L..,Bedo J..,McCabe M.J..,Pajic M..,...&Thomas D.M..(2020).MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer.,368(6495).
MLA	Cipponi A.,et al."MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer".368.6495(2020).