气候变化领域集成服务门户(CCPortal): Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11

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DOI	10.1073/pnas.2021475118
	Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11
	Mukhopadhyay S.; Biancur D.E.; Parker S.J.; Yamamoto K.; Banh R.S.; Paulo J.A.; Mancias J.D.; Kimmelman A.C.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is highly refractory to current therapies. We had previously shown that PDAC can utilize its high levels of basal autophagy to support its metabolism and maintain tumor growth. Consistent with the importance of autophagy in PDAC, autophagy inhibition significantly enhances response of PDAC patients to chemotherapy in two randomized clinical trials. However, the specific metabolite(s) that autophagy provides to support PDAC growth is not yet known. In this study, we demonstrate that under nutrient-replete conditions, loss of autophagy in PDAC leads to a relatively restricted impairment of amino acid pools, with cysteine levels showing a significant drop. Additionally, we made the striking discovery that autophagy is critical for the proper membrane localization of the cystine transporter SLC7A11. Mechanistically, autophagy impairment results in the loss of SLC7A11 on the plasma membrane and increases its localization at the lysosome in an mTORC2-dependent manner. Our results demonstrate a critical link between autophagy and cysteine metabolism and provide mechanistic insights into how targeting autophagy can cause metabolic dysregulation in PDAC. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autophagy; Lysosome; Pancreatic cancer; Pancreatic ductal adenocarcinoma; SLC7A11
语种	英语
scopus关键词	amino acid transporter; cysteine; mammalian target of rapamycin complex 2; SLC7A11 protein; unclassified drug; amino acid metabolism; Article; autophagy (cellular); cell membrane; cellular distribution; controlled study; human; human cell; lysosome; pancreas adenocarcinoma; priority journal; protein localization; regulatory mechanism
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/180717
作者单位	Laura and Isaac Perlmutter Cancer Center, Department of Radiation Oncology, New York University, School of Medicine, New York, NY 10016, United States; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States
推荐引用方式 GB/T 7714	Mukhopadhyay S.,Biancur D.E.,Parker S.J.,et al. Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11[J],2021,118(6).
APA	Mukhopadhyay S..,Biancur D.E..,Parker S.J..,Yamamoto K..,Banh R.S..,...&Kimmelman A.C..(2021).Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Mukhopadhyay S.,et al."Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).