{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:54:13Z","timestamp":1791140053341,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"20","license":[{"start":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T00:00:00Z","timestamp":1341792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T00:00:00Z","timestamp":1341792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2013,5,16]]},"DOI":"10.1038\/onc.2012.277","type":"journal-article","created":{"date-parts":[[2012,7,9]],"date-time":"2012-07-09T14:44:41Z","timestamp":1341845081000},"page":"2543-2554","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Autophagy restricts proliferation driven by oncogenic phosphatidylinositol 3-kinase in three-dimensional culture"],"prefix":"10.1038","volume":"32","author":[{"given":"N","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Eritja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Lock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Debnath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,7,9]]},"reference":[{"key":"BFonc2012277_CR1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","volume":"43","author":"C He","year":"2009","unstructured":"He C, Klionsky DJ . Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009; 43: 67\u201393.","journal-title":"Annu Rev Genet"},{"key":"BFonc2012277_CR2","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/nrc1692","volume":"5","author":"Y Kondo","year":"2005","unstructured":"Kondo Y, Kanzawa T, Sawaya R, Kondo S . The role of autophagy in cancer development and response to therapy. Nat Rev Cancer 2005; 5: 726\u2013734.","journal-title":"Nat Rev Cancer"},{"key":"BFonc2012277_CR3","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1016\/j.febslet.2009.12.034","volume":"584","author":"N Chen","year":"2010","unstructured":"Chen N, Debnath J . Autophagy and tumorigenesis. FEBS Lett 2010; 584: 1427\u20131435.","journal-title":"FEBS Lett"},{"key":"BFonc2012277_CR4","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/45257","volume":"402","author":"XH Liang","year":"1999","unstructured":"Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672\u2013676.","journal-title":"Nature"},{"key":"BFonc2012277_CR5","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1172\/JCI20039","volume":"112","author":"X Qu","year":"2003","unstructured":"Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003; 112: 1809\u20131820.","journal-title":"J Clin Invest"},{"key":"BFonc2012277_CR6","doi-asserted-by":"publisher","first-page":"15077","DOI":"10.1073\/pnas.2436255100","volume":"100","author":"Z Yue","year":"2003","unstructured":"Yue Z, Jin S, Yang C, Levine AJ, Heintz N . Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 2003; 100: 15077\u201315082.","journal-title":"Proc Natl Acad Sci USA."},{"key":"BFonc2012277_CR7","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1083\/jcb.201102031","volume":"193","author":"Y Inami","year":"2011","unstructured":"Inami Y, Waguri S, Sakamoto A, Kouno T, Nakada K, Hino O et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J Cell Biol 2011; 193: 275\u2013284.","journal-title":"J Cell Biol"},{"key":"BFonc2012277_CR8","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1101\/gad.2016211","volume":"25","author":"A Takamura","year":"2011","unstructured":"Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S et al. Autophagy-deficient mice develop multiple liver tumors. Genes Dev 2011; 25: 795\u2013800.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR9","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1101\/gad.1565707","volume":"21","author":"V Karantza-Wadsworth","year":"2007","unstructured":"Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 2007; 21: 1621\u20131635.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR10","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1101\/gad.1545107","volume":"21","author":"R Mathew","year":"2007","unstructured":"Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 2007; 21: 1367\u20131381.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR11","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1126\/science.1096502","volume":"304","author":"Y Samuels","year":"2004","unstructured":"Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004; 304: 554.","journal-title":"Science"},{"key":"BFonc2012277_CR12","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1073\/pnas.0408864102","volume":"102","author":"S Kang","year":"2005","unstructured":"Kang S, Bader AG, Vogt PK . Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA. 2005; 102: 802\u2013807.","journal-title":"Proc Natl Acad Sci USA."},{"key":"BFonc2012277_CR13","doi-asserted-by":"publisher","first-page":"10992","DOI":"10.1158\/0008-5472.CAN-05-2612","volume":"65","author":"SJ Isakoff","year":"2005","unstructured":"Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV et al. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 2005; 65: 10992\u201311000.","journal-title":"Cancer Res"},{"key":"BFonc2012277_CR14","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/S1046-2023(03)00032-X","volume":"30","author":"J Debnath","year":"2003","unstructured":"Debnath J, Muthuswamy SK, Brugge JS . Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 2003; 30: 256\u2013268.","journal-title":"Methods"},{"key":"BFonc2012277_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0092-8674(02)01001-2","volume":"111","author":"J Debnath","year":"2002","unstructured":"Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS . The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 2002; 111: 29\u201340.","journal-title":"Cell"},{"key":"BFonc2012277_CR16","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1074\/jbc.275.2.992","volume":"275","author":"A Petiot","year":"2000","unstructured":"Petiot A, Ogier-Denis E, Blommaart EF, Meijer AJ, Codogno P . Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 2000; 275: 992\u2013998.","journal-title":"J Biol Chem"},{"key":"BFonc2012277_CR17","doi-asserted-by":"publisher","first-page":"151","DOI":"10.4161\/auto.5338","volume":"4","author":"DJ Klionsky","year":"2008","unstructured":"Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 2008; 4: 151\u2013175.","journal-title":"Autophagy"},{"key":"BFonc2012277_CR18","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1091\/mbc.e07-10-1092","volume":"19","author":"C Fung","year":"2008","unstructured":"Fung C, Lock R, Gao S, Salas E, Debnath J . Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol Cell 2008; 19: 797\u2013806.","journal-title":"Mol Biol Cell"},{"key":"BFonc2012277_CR19","doi-asserted-by":"publisher","first-page":"8452","DOI":"10.1074\/jbc.M306337200","volume":"279","author":"T Kanazawa","year":"2004","unstructured":"Kanazawa T, Taneike I, Akaishi R, Yoshizawa F, Furuya N, Fujimura S et al. Amino acids and insulin control autophagic proteolysis through different signaling pathways in relation to mTOR in isolated rat hepatocytes. J Biol Chem 2004; 279: 8452\u20138459.","journal-title":"J Biol Chem"},{"key":"BFonc2012277_CR20","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1083\/jcb.200304159","volume":"163","author":"J Debnath","year":"2003","unstructured":"Debnath J, Walker SJ, Brugge JS . Akt activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner. J Cell Biol 2003; 163: 315\u2013326.","journal-title":"J Cell Biol"},{"key":"BFonc2012277_CR21","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/j.1432-1033.1996.00564.x-i2","volume":"235","author":"JJ Luiken","year":"1996","unstructured":"Luiken JJ, Aerts JM, Meijer AJ . The role of the intralysosomal pH in the control of autophagic proteolytic flux in rat hepatocytes. Eur J Biochem 1996; 235: 564\u2013573.","journal-title":"Eur J Biochem"},{"key":"BFonc2012277_CR22","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1158\/1078-0432.CCR-10-2634","volume":"17","author":"RK Amaravadi","year":"2011","unstructured":"Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res 2011; 17: 654\u2013666.","journal-title":"Clin Cancer Res"},{"key":"BFonc2012277_CR23","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nrc1695","volume":"5","author":"J Debnath","year":"2005","unstructured":"Debnath J, Brugge JS . Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer 2005; 5: 675\u2013688.","journal-title":"Nat Rev Cancer"},{"key":"BFonc2012277_CR24","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1083\/jcb.200507002","volume":"171","author":"G Bjorkoy","year":"2005","unstructured":"Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A et al. p62\/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 2005; 171: 603\u2013614.","journal-title":"J Cell Biol"},{"key":"BFonc2012277_CR25","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.cell.2009.03.048","volume":"137","author":"R Mathew","year":"2009","unstructured":"Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY et al. Autophagy suppresses tumorigenesis through elimination of p62. Cell 2009; 137: 1062\u20131075.","journal-title":"Cell"},{"key":"BFonc2012277_CR26","doi-asserted-by":"publisher","first-page":"24131","DOI":"10.1074\/jbc.M702824200","volume":"282","author":"S Pankiv","year":"2007","unstructured":"Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H et al. p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131\u201324145.","journal-title":"J Biol Chem"},{"key":"BFonc2012277_CR27","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1101\/gad.17558811","volume":"25","author":"AC Kimmelman","year":"2011","unstructured":"Kimmelman AC . The dynamic nature of autophagy in cancer. Genes Dev 2011; 25: 1999\u20132010.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR28","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1101\/gad.2016311","volume":"25","author":"JY Guo","year":"2011","unstructured":"Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 2011; 25: 460\u2013470.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR29","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1101\/gad.2016111","volume":"25","author":"S Yang","year":"2011","unstructured":"Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011; 25: 717\u2013729.","journal-title":"Genes Dev"},{"key":"BFonc2012277_CR30","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1091\/mbc.e10-06-0500","volume":"22","author":"R Lock","year":"2011","unstructured":"Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM et al. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 2011; 22: 165\u2013178.","journal-title":"Mol Biol Cell"},{"key":"BFonc2012277_CR31","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S0076-6879(08)03625-2","volume":"452","author":"J Debnath","year":"2009","unstructured":"Debnath J . Detachment-induced autophagy in three-dimensional epithelial cell cultures. Methods Enzymol 2009; 452: 423\u2013439.","journal-title":"Methods Enzymol"},{"key":"BFonc2012277_CR32","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/nrc2664","volume":"9","author":"JA Engelman","year":"2009","unstructured":"Engelman JA . Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009; 9: 550\u2013562.","journal-title":"Nat Rev Cancer"},{"key":"BFonc2012277_CR33","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrclinonc.2011.71","volume":"8","author":"F Janku","year":"2011","unstructured":"Janku F, McConkey DJ, Hong DS, Kurzrock R . Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol 2011; 8: 528\u2013539.","journal-title":"Nat Rev Clin Oncol"},{"key":"BFonc2012277_CR34","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cell.2011.10.021","volume":"147","author":"J Moscat","year":"2011","unstructured":"Moscat J, Diaz-Meco MT . Feedback on fat: p62-mTORC1-autophagy connections. Cell 2011; 147: 724\u2013727.","journal-title":"Cell"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/onc2012277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/onc2012277","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/onc2012277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T18:14:11Z","timestamp":1647886451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/onc2012277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,9]]},"references-count":34,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2013,5,16]]}},"alternative-id":["BFonc2012277"],"URL":"https:\/\/doi.org\/10.1038\/onc.2012.277","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,9]]},"assertion":[{"value":"9 February 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2012","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}