气候变化领域集成服务门户(CCPortal): NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition

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DOI	10.1073/pnas.2012469118
	NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition
	Moore A.M.; Zhou L.; Cui J.; Li L.; Wu N.; Yu A.; Poddar S.; Liang K.; Abt E.R.; Kim S.; Ghukasyan R.; Khachatourian N.; Pagano K.; Elliott I.; Dann A.M.; Riahi R.; Le T.; Dawson D.W.; Radu C.G.; Donahue T.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14. Their individual contributions to this mechanism in PDAC have not been previously delineated. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway, a dominant source of NAD in cancer cells. We found that IFN-induced NAD consumption increased dependence upon NAMPT for its role in recycling NAM to salvage NAD pools, thus sensitizing PDAC cells to pharmacologic NAMPT inhibition. Their combination decreased PDAC cell proliferation and invasion in vitro and suppressed orthotopic tumor growth and liver metastases in vivo. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Interferon; NAD; NAMPT; Pancreatic cancer; PARP
语种	英语
scopus关键词	interferon; nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 10; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 14; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 9; nicotinamide phosphoribosyltransferase; unclassified drug; animal experiment; animal model; Article; cancer cell; cancer growth; cell invasion; cell proliferation; controlled study; depletion; enzyme inhibition; human; human cell; human tissue; immunohistochemistry; in vitro study; in vivo study; liver metastasis; mouse; nonhuman; pancreas adenocarcinoma; priority journal; protein expression; real time polymerase chain reaction; sensitization; signal transduction; upregulation; Western blotting
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/180566
作者单位	Department of Surgery, University of California, Los Angeles, CA 90095, United States; David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States; Department of Pancreatic and Thyroidal Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China; Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, 430022, China; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, United States; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095, United States; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, United States; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, United States
推荐引用方式 GB/T 7714	Moore A.M.,Zhou L.,Cui J.,et al. NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition[J],2021,118(8).
APA	Moore A.M..,Zhou L..,Cui J..,Li L..,Wu N..,...&Donahue T.R..(2021).NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Moore A.M.,et al."NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).