气候变化领域集成服务门户(CCPortal): Cysteine depletion induces pancreatic tumor ferroptosis in mice

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DOI	10.1126/science.aaw9872
	Cysteine depletion induces pancreatic tumor ferroptosis in mice
	Badgley M.A.; Kremer D.M.; Carlo Maurer H.; DelGiorno K.E.; Lee H.-J.; Purohit V.; Sagalovskiy I.R.; Ma A.; Kapilian J.; Firl C.E.M.; Decker A.R.; Sastra S.A.; Palermo C.F.; Andrade L.R.; Sajjakulnukit P.; Zhang L.; Tolstyka Z.P.; Hirschhorn T.; Lamb C.; Liu T.; Gu W.; Scott Seeley E.; Stone E.; Georgiou G.; Manor U.; Iuga A.; Wahl G.M.; Stockwell B.R.; Lyssiotis C.A.; Olive K.P.
发表日期	2020
ISSN	0036-8075
卷号	368 期号:6486
英文摘要	Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid reactive oxygen species (ROS). Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. In this work, we show that the import of oxidized cysteine (cystine) via system xC - is a critical dependency of pancreatic ductal adenocarcinoma (PDAC), which is a leading cause of cancer mortality. PDAC cells used cysteine to synthesize glutathione and coenzyme A, which, together, down-regulated ferroptosis. Studying genetically engineered mice, we found that the deletion of a system xC - subunit, Slc7a11, induced tumor-selective ferroptosis and inhibited PDAC growth. This was replicated through the administration of cyst(e)inase, a drug that depletes cysteine and cystine, demonstrating a translatable means to induce ferroptosis in PDAC. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	coenzyme A cysteine glutathione amino acid induced response rodent tumor animal experiment animal model animal tissue Article cell death cell survival cell viability controlled study down regulation ferroptosis fragmentation reaction human human cell lipid oxidation lipophilicity mouse necroptosis nonhuman pancreas tumor pancreatic ductal carcinoma cell line priority journal protein cleavage protein expression tumor growth tumor microenvironment tumor xenograft Mus
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133585
推荐引用方式 GB/T 7714	Badgley M.A.,Kremer D.M.,Carlo Maurer H.,et al. Cysteine depletion induces pancreatic tumor ferroptosis in mice[J]. Science,2020,368(6486).
APA	Badgley M.A..,Kremer D.M..,Carlo Maurer H..,DelGiorno K.E..,Lee H.-J..,...&Olive K.P..(2020).Cysteine depletion induces pancreatic tumor ferroptosis in mice.,368(6486).
MLA	Badgley M.A.,et al."Cysteine depletion induces pancreatic tumor ferroptosis in mice".368.6486(2020).