{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:26:17Z","timestamp":1792790777845,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"7732","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1038\/s41586-018-0697-7","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T07:03:12Z","timestamp":1542092592000},"page":"569-573","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":330,"title":["Autophagy maintains tumour growth through circulating arginine"],"prefix":"10.1038","volume":"563","author":[{"given":"Laura","family":"Poillet-Perez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian Sherrie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Maganti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherry","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus W.","family":"Bosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Mehnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie Yanxiang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Lattime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Rabinowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"697_CR1","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1158\/2159-8290.CD-14-0363","volume":"4","author":"G Karsli-Uzunbas","year":"2014","unstructured":"Karsli-Uzunbas, G. et al. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov. 4, 914\u2013927 (2014).","journal-title":"Cancer Discov."},{"key":"697_CR2","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1083\/jcb.200412022","volume":"169","author":"M Komatsu","year":"2005","unstructured":"Komatsu, M. et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425\u2013434 (2005).","journal-title":"J. Cell Biol."},{"key":"697_CR3","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/nature03029","volume":"432","author":"A Kuma","year":"2004","unstructured":"Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032\u20131036 (2004).","journal-title":"Nature"},{"key":"697_CR4","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1101\/gad.283416.116","volume":"30","author":"JY Guo","year":"2016","unstructured":"Guo, J. Y. et al. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells. Genes Dev. 30, 1704\u20131717 (2016).","journal-title":"Genes Dev."},{"key":"697_CR5","first-page":"73","volume":"279","author":"Y Kamada","year":"2004","unstructured":"Kamada, Y., Sekito, T. & Ohsumi, Y. Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr. Top. Microbiol. Immunol. 279, 73\u201384 (2004).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"697_CR6","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/j.cmet.2017.04.004","volume":"25","author":"AC Kimmelman","year":"2017","unstructured":"Kimmelman, A. C. & White, E. Autophagy and tumor metabolism. Cell Metab. 25, 1037\u20131043 (2017).","journal-title":"Cell Metab."},{"key":"697_CR7","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1101\/gad.287524.116","volume":"30","author":"R Amaravadi","year":"2016","unstructured":"Amaravadi, R., Kimmelman, A. C. & White, E. Recent insights into the function of autophagy in cancer. Genes Dev. 30, 1913\u20131930 (2016).","journal-title":"Genes Dev."},{"key":"697_CR8","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1158\/2159-8290.CD-17-0952","volume":"8","author":"A Yang","year":"2018","unstructured":"Yang, A. et al. Autophagy sustains pancreatic cancer growth through both cell-autonomous and nonautonomous mechanisms. Cancer Discov. 8, 276\u2013287 (2018).","journal-title":"Cancer Discov."},{"key":"697_CR9","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/pcmr.12591","volume":"30","author":"J Wang","year":"2017","unstructured":"Wang, J. et al. UV-induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell Melanoma Res. 30, 428\u2013435 (2017).","journal-title":"Pigment Cell Melanoma Res."},{"key":"697_CR10","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1158\/2159-8290.CD-13-0397","volume":"3","author":"AM Strohecker","year":"2013","unstructured":"Strohecker, A. M. et al. Autophagy sustains mitochondrial glutamine metabolism and growth of Braf V600E-driven lung tumors. Cancer Discov. 3, 1272\u20131285 (2013).","journal-title":"Cancer Discov."},{"key":"697_CR11","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1101\/gad.219642.113","volume":"27","author":"JY Guo","year":"2013","unstructured":"Guo, J. Y. et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 27, 1447\u20131461 (2013).","journal-title":"Genes Dev."},{"key":"697_CR12","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cell.2016.02.035","volume":"165","author":"L Chantranupong","year":"2016","unstructured":"Chantranupong, L. et al. The CASTOR proteins are arginine sensors for the mTORC1 Pathway. Cell 165, 153\u2013164 (2016).","journal-title":"Cell"},{"key":"697_CR13","doi-asserted-by":"publisher","first-page":"1602S","DOI":"10.1093\/jn\/137.6.1602S","volume":"137","author":"SM Morris Jr.","year":"2007","unstructured":"Morris, S. M. Jr. Arginine metabolism: boundaries of our knowledge. J. Nutr. 137, 1602S\u20131609S (2007).","journal-title":"J. Nutr."},{"key":"697_CR14","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1002\/ijc.25202","volume":"126","author":"B Delage","year":"2010","unstructured":"Delage, B. et al. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int. J. Cancer 126, 2762\u20132772 (2010).","journal-title":"Int. J. Cancer"},{"key":"697_CR15","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/cncr.20057","volume":"100","author":"BJ Dillon","year":"2004","unstructured":"Dillon, B. J. et al. Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer 100, 826\u2013833 (2004).","journal-title":"Cancer"},{"key":"697_CR16","doi-asserted-by":"publisher","first-page":"4957","DOI":"10.1038\/onc.2016.37","volume":"35","author":"MD Patil","year":"2016","unstructured":"Patil, M. D., Bhaumik, J., Babykutty, S., Banerjee, U. C. & Fukumura, D. Arginine dependence of tumor cells: targeting a chink in cancer\u2019s armor. Oncogene 35, 4957\u20134972 (2016).","journal-title":"Oncogene"},{"key":"697_CR17","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/nature15529","volume":"527","author":"S Rabinovich","year":"2015","unstructured":"Rabinovich, S. et al. Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. Nature 527, 379\u2013383 (2015).","journal-title":"Nature"},{"key":"697_CR18","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2015.1127314","volume":"3","author":"SC Nagamani","year":"2016","unstructured":"Nagamani, S. C. & Erez, A. A metabolic link between the urea cycle and cancer cell proliferation. Mol. Cell. Oncol. 3, e1127314 (2016).","journal-title":"Mol. Cell. Oncol."},{"key":"697_CR19","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/bjc.2012.106","volume":"106","author":"LG Feun","year":"2012","unstructured":"Feun, L. G. et al. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase. Br. J. Cancer 106, 1481\u20131485 (2012).","journal-title":"Br. J. Cancer"},{"key":"697_CR20","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1111\/j.1755-148X.2010.00798.x","volume":"24","author":"TL Lam","year":"2011","unstructured":"Lam, T. L. et al. Recombinant human arginase inhibits the in vitro and in vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis. Pigment Cell Melanoma Res. 24, 366\u2013376 (2011).","journal-title":"Pigment Cell Melanoma Res."},{"key":"697_CR21","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nature24057","volume":"551","author":"S Hui","year":"2017","unstructured":"Hui, S. et al. Glucose feeds the TCA cycle via circulating lactate. Nature 551, 115\u2013118 (2017).","journal-title":"Nature"},{"key":"697_CR22","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/MCO.0b013e32834d1a08","volume":"15","author":"SM Morris Jr.","year":"2012","unstructured":"Morris, S. M. Jr. Arginases and arginine deficiency syndromes. Curr. Opin. Clin. Nutr. Metab. Care 15, 64\u201370 (2012).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"697_CR23","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1101\/gad.2016211","volume":"25","author":"A Takamura","year":"2011","unstructured":"Takamura, A. et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 25, 795\u2013800 (2011).","journal-title":"Genes Dev."},{"key":"697_CR24","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","volume":"131","author":"M Komatsu","year":"2007","unstructured":"Komatsu, M. et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149\u20131163 (2007).","journal-title":"Cell"},{"key":"697_CR25","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nature19084","volume":"536","author":"CM Sousa","year":"2016","unstructured":"Sousa, C. M. et al. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 536, 479\u2013483 (2016).","journal-title":"Nature"},{"key":"697_CR26","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature20815","volume":"541","author":"NS Katheder","year":"2017","unstructured":"Katheder, N. S. et al. Microenvironmental autophagy promotes tumour growth. Nature 541, 417\u2013420 (2017).","journal-title":"Nature"},{"key":"697_CR27","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.celrep.2016.12.077","volume":"18","author":"JC Kremer","year":"2017","unstructured":"Kremer, J. C. et al. Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Reports 18, 991\u20131004 (2017).","journal-title":"Cell Reports"},{"key":"697_CR28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10637-012-9807-9","volume":"31","author":"T Yau","year":"2013","unstructured":"Yau, T. et al. A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma. Invest. New Drugs 31, 99\u2013107 (2013).","journal-title":"Invest. New Drugs"},{"key":"697_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.137","volume":"8","author":"W Shen","year":"2017","unstructured":"Shen, W. et al. A novel and promising therapeutic approach for NSCLC: recombinant human arginase alone or combined with autophagy inhibitor. Cell Death Dis. 8, e2720 (2017).","journal-title":"Cell Death Dis."},{"key":"697_CR30","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.2147\/OTT.S106810","volume":"10","author":"J Koprivnikar","year":"2017","unstructured":"Koprivnikar, J., McCloskey, J. & Faderl, S. Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia. Onco Targets Ther. 10, 1413\u20131422 (2017).","journal-title":"Onco Targets Ther."},{"key":"697_CR31","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.stem.2007.03.002","volume":"1","author":"Y Ruzankina","year":"2007","unstructured":"Ruzankina, Y. et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1, 113\u2013126 (2007).","journal-title":"Cell Stem Cell"},{"key":"697_CR32","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature04724","volume":"441","author":"T Hara","year":"2006","unstructured":"Hara, T. et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885\u2013889 (2006).","journal-title":"Nature"},{"key":"697_CR33","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1111\/pcmr.12498","volume":"29","author":"K Meeth","year":"2016","unstructured":"Meeth, K., Wang, J. X., Micevic, G., Damsky, W. & Bosenberg, M. W. The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations. Pigment Cell Melanoma Res. 29, 590\u2013597 (2016).","journal-title":"Pigment Cell Melanoma Res."},{"key":"697_CR34","first-page":"1017","volume":"62","author":"IC Summerhayes","year":"1979","unstructured":"Summerhayes, I. C. & Franks, L. M. Effects of donor age on neoplastic transformation of adult mouse bladder epithelium in vitro. J. Natl. Cancer Inst. 62, 1017\u20131023 (1979).","journal-title":"in vitro. J. Natl. Cancer Inst."},{"key":"697_CR35","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.1021\/ac902837x","volume":"82","author":"W Lu","year":"2010","unstructured":"Lu, W. et al. Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. Anal. Chem. 82, 3212\u20133221 (2010).","journal-title":"Anal. Chem."},{"key":"697_CR36","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.cmet.2016.10.012","volume":"24","author":"R Papazyan","year":"2016","unstructured":"Papazyan, R. et al. Physiological suppression of lipotoxic liver damage by complementary actions of HDAC3 and SCAP\/SREBP. Cell Metab. 24, 863\u2013874 (2016).","journal-title":"Cell Metab."},{"key":"697_CR37","doi-asserted-by":"publisher","first-page":"9818","DOI":"10.1021\/ac1021166","volume":"82","author":"E Melamud","year":"2010","unstructured":"Melamud, E., Vastag, L. & Rabinowitz, J. D. Metabolomic analysis and visualization engine for LC\u2013MS data. Anal. Chem. 82, 9818\u20139826 (2010).","journal-title":"Anal. Chem."},{"key":"697_CR38","doi-asserted-by":"publisher","first-page":"G93","DOI":"10.1152\/ajpgi.00252.2015","volume":"310","author":"L Zhan","year":"2016","unstructured":"Zhan, L. et al. Dysregulation of bile acid homeostasis in parenteral nutrition mouse model. Am. J. Physiol. Gastrointest. Liver Physiol. 310, G93\u2013G102 (2016).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"697_CR39","doi-asserted-by":"publisher","first-page":"5940","DOI":"10.1021\/acs.analchem.7b00396","volume":"89","author":"X Su","year":"2017","unstructured":"Su, X., Lu, W. & Rabinowitz, J. D. Metabolite spectral accuracy on orbitraps. Anal. Chem. 89, 5940\u20135948 (2017).","journal-title":"Anal. Chem."},{"key":"697_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063950","volume":"8","author":"M Sailer","year":"2013","unstructured":"Sailer, M. et al. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome. PLoS ONE 8, e63950 (2013).","journal-title":"PLoS ONE"},{"key":"697_CR41","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1074\/mcp.M900122-MCP200","volume":"8","author":"DE Sleat","year":"2009","unstructured":"Sleat, D. E. et al. Mass spectrometry-based protein profiling to determine the cause of lysosomal storage diseases of unknown etiology. Mol. Cell. Proteomics 8, 1708\u20131718 (2009).","journal-title":"Mol. Cell. Proteomics"},{"key":"697_CR42","first-page":"217","volume":"328","author":"RC Beavis","year":"2006","unstructured":"Beavis, R. C. Using the global proteome machine for protein identification. Methods Mol. Biol. 328, 217\u2013228 (2006).","journal-title":"Methods Mol. Biol."},{"key":"697_CR43","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1515\/1544-6115.1826","volume":"11","author":"SP Lund","year":"2012","unstructured":"Lund, S. P., Nettleton, D., McCarthy, D. J. & Smyth, G. K. Detecting differential expression in RNA-sequence data using quasi-likelihood with shrunken dispersion estimates. Stat. Appl. Genet. Mol. Biol. 11, 1544-6115 (2012).","journal-title":"Stat. Appl. Genet. Mol. Biol."}],"updated-by":[{"DOI":"10.1038\/s41586-018-0815-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T00:00:00Z","timestamp":1544054400000}}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0697-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0697-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0697-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T05:45:32Z","timestamp":1720763132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-018-0697-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":43,"journal-issue":{"issue":"7732","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["697"],"URL":"https:\/\/doi.org\/10.1038\/s41586-018-0697-7","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"3 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In this Letter, \u2018released\u2019 should have been \u2018regulated\u2019 in the sentence starting: \u2018Deletion of <i>Atg5<\/i> in the host similarly regulated circulating arginine and suppressed tumorigenesis...\u2019 This has been corrected online.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"E.W. is co-founder of Vescor Therapeutics. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}