{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:49:07Z","timestamp":1791226147470,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"14","license":[{"start":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T00:00:00Z","timestamp":1580947200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T00:00:00Z","timestamp":1580947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2020,4,2]]},"DOI":"10.1038\/s41388-020-1194-7","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T14:04:20Z","timestamp":1580997860000},"page":"2921-2933","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["ERBB3-induced furin promotes the progression and metastasis of ovarian cancer via the IGF1R\/STAT3 signaling axis"],"prefix":"10.1038","volume":"39","author":[{"given":"Changliang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-8950","authenticated-orcid":false,"given":"Deepak","family":"Parashar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopakumar G.","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Geethadevi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirng-Wern","family":"Tsaih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3555-6119","authenticated-orcid":false,"given":"Ramani","family":"Ramchandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7031-3385","authenticated-orcid":false,"given":"Janet S.","family":"Rader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Chaluvally-Raghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunila","family":"Pradeep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"1194_CR1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrclinonc.2013.5","volume":"10","author":"RL Coleman","year":"2013","unstructured":"Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 2013;10:211\u201324.","journal-title":"Nat Rev Clin Oncol"},{"key":"1194_CR2","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3322\/caac.21456","volume":"68","author":"LA Torre","year":"2018","unstructured":"Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68:284\u201396.","journal-title":"CA Cancer J Clin"},{"key":"1194_CR3","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/ijc.31063","volume":"142","author":"K Gaitskell","year":"2018","unstructured":"Gaitskell K, Green J, Pirie K, Barnes I, Hermon C, Reeves GK, et al. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the prospective Million Women Study. Int J Cancer. 2018;142:281\u20139.","journal-title":"Int J Cancer"},{"key":"1194_CR4","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1038\/onc.2016.323","volume":"36","author":"D Fang","year":"2017","unstructured":"Fang D, Chen H, Zhu JY, Wang W, Teng Y, Ding HF, et al. Epithelial-mesenchymal transition of ovarian cancer cells is sustained by Rac1 through simultaneous activation of MEK1\/2 and Src signaling pathways. Oncogene. 2017;36:1546\u201358.","journal-title":"Oncogene."},{"key":"1194_CR5","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nrclinonc.2009.62","volume":"6","author":"H Linardou","year":"2009","unstructured":"Linardou H, Dahabreh IJ, Bafaloukos D, Kosmidis P, Murray S. Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol. 2009;6:352\u201366.","journal-title":"Nat Rev Clin Oncol"},{"key":"1194_CR6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","volume":"378","author":"JC Soria","year":"2018","unstructured":"Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N. Engl J Med. 2018;378:113\u201325.","journal-title":"N. Engl J Med"},{"key":"1194_CR7","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/431525b","volume":"431","author":"P Stephens","year":"2004","unstructured":"Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature. 2004;431:525\u20136.","journal-title":"Nature."},{"key":"1194_CR8","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1126\/science.1141478","volume":"316","author":"JA Engelman","year":"2007","unstructured":"Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039\u201343.","journal-title":"Science."},{"key":"1194_CR9","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1158\/0008-5472.CAN-04-3150","volume":"65","author":"TT Junttila","year":"2005","unstructured":"Junttila TT, Sundvall M, Lundin M, Lundin J, Tanner M, Harkonen P, et al. Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells. Cancer Res. 2005;65:1384\u201393.","journal-title":"Cancer Res."},{"key":"1194_CR10","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/35052073","volume":"2","author":"Y Yarden","year":"2001","unstructured":"Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127\u201337.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1194_CR11","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ccr.2014.05.002","volume":"26","author":"S Pradeep","year":"2014","unstructured":"Pradeep S, Kim SW, Wu SY, Nishimura M, Chaluvally-Raghavan P, Miyake T, et al. Hematogenous metastasis of ovarian cancer: rethinking mode of spread. Cancer Cell. 2014;26:77\u201391.","journal-title":"Cancer Cell."},{"key":"1194_CR12","doi-asserted-by":"crossref","first-page":"746","DOI":"10.18632\/genesandcancer.162","volume":"8","author":"A Geethadevi","year":"2017","unstructured":"Geethadevi A, Parashar D, Bishop E, Pradeep S, Chaluvally-Raghavan P. ERBB signaling in CTCs of ovarian cancer and glioblastoma. Genes Cancer. 2017;8:746\u201351.","journal-title":"Genes Cancer."},{"key":"1194_CR13","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1002\/ijc.30714","volume":"141","author":"P Jaaks","year":"2017","unstructured":"Jaaks P, Bernasconi M. The proprotein convertase furin in tumour progression. Int J Cancer. 2017;141:654\u201363.","journal-title":"Int J Cancer"},{"key":"1194_CR14","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nrm934","volume":"3","author":"G Thomas","year":"2002","unstructured":"Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol cell Biol. 2002;3:753\u201366.","journal-title":"Nat Rev Mol cell Biol"},{"key":"1194_CR15","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.1158\/1078-0432.CCR-03-0801","volume":"10","author":"R Hassan","year":"2004","unstructured":"Hassan R, Bera T, Pastan I. Mesothelin: a new target for immunotherapy. Clin Cancer Res. 2004;10:3937\u201342.","journal-title":"Clin Cancer Res"},{"key":"1194_CR16","doi-asserted-by":"publisher","first-page":"10326","DOI":"10.1073\/pnas.191199198","volume":"98","author":"DE Bassi","year":"2001","unstructured":"Bassi DE, Lopez De Cicco R, Mahloogi H, Zucker S, Thomas G, Klein-Szanto AJ. Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells. Proc Natl Acad Sci USA. 2001;98:10326\u201331.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1194_CR17","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/S0002-9440(10)63838-2","volume":"162","author":"DE Bassi","year":"2003","unstructured":"Bassi DE, Mahloogi H, Lopez De Cicco R, Klein-Szanto A. Increased furin activity enhances the malignant phenotype of human head and neck cancer cells. Am J Pathol. 2003;162:439\u201347.","journal-title":"Am J Pathol"},{"key":"1194_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033414","volume":"7","author":"YC Ma","year":"2012","unstructured":"Ma YC, Shi C, Zhang YN, Wang LG, Liu H, Jia HT, et al. The tyrosine kinase c-Src directly mediates growth factor-induced Notch-1 and Furin interaction and Notch-1 activation in pancreatic cancer cells. PLoS ONE. 2012;7:e33414.","journal-title":"PLoS ONE"},{"key":"1194_CR19","doi-asserted-by":"publisher","first-page":"11830","DOI":"10.1158\/0008-5472.CAN-07-1160","volume":"67","author":"T Wang","year":"2007","unstructured":"Wang T, Zhao J, Ren JL, Zhang L, Wen WH, Zhang R, et al. Recombinant immunoproapoptotic proteins with furin site can translocate and kill HER2-positive cancer cells. Cancer Res. 2007;67:11830\u20139.","journal-title":"Cancer Res."},{"key":"1194_CR20","first-page":"289","volume":"29","author":"RE Page","year":"2007","unstructured":"Page RE, Klein-Szanto AJ, Litwin S, Nicolas E, Al-Jumaily R, Alexander P, et al. Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer. Cell Oncol. 2007;29:289\u201399.","journal-title":"Cell Oncol"},{"key":"1194_CR21","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1530\/ERC-11-0329","volume":"19","author":"B Gyorffy","year":"2012","unstructured":"Gyorffy B, Lanczky A, Szallasi Z. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012;19:197\u2013208.","journal-title":"Endocr Relat Cancer"},{"key":"1194_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29142-x","volume":"8","author":"JH Lee","year":"2018","unstructured":"Lee JH, Choi SI, Kim RK, Cho EW, Kim IG. Tescalcin\/c-Src\/IGF1Rbeta-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1. Sci Rep. 2018;8:10711.","journal-title":"Sci Rep."},{"key":"1194_CR23","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0092-8674(00)81959-5","volume":"98","author":"JF Bromberg","year":"1999","unstructured":"Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98:295\u2013303.","journal-title":"Cell."},{"key":"1194_CR24","doi-asserted-by":"publisher","first-page":"626","DOI":"10.2174\/156652409788488720","volume":"9","author":"E Devarajan","year":"2009","unstructured":"Devarajan E, Huang S. STAT3 as a central regulator of tumor metastases. Curr Mol Med. 2009;9:626\u201333.","journal-title":"Curr Mol Med"},{"key":"1194_CR25","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1002\/stem.1609","volume":"32","author":"G Huang","year":"2014","unstructured":"Huang G, Yan H, Ye S, Tong C, Ying QL. STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates mouse ESC fates. Stem Cells. 2014;32:1149\u201360.","journal-title":"Stem Cells."},{"key":"1194_CR26","doi-asserted-by":"publisher","first-page":"6074","DOI":"10.1128\/JVI.68.9.6074-6078.1994","volume":"68","author":"T Horimoto","year":"1994","unstructured":"Horimoto T, Nakayama K, Smeekens SP, Kawaoka Y. Proprotein-processing endoproteases PC6 and furin both activate hemagglutinin of virulent avian influenza viruses. J Virol. 1994;68:6074\u20138.","journal-title":"J Virol"},{"key":"1194_CR27","doi-asserted-by":"publisher","first-page":"111503","DOI":"10.1016\/j.yexcr.2019.111503","volume":"383","author":"J Baumann","year":"2019","unstructured":"Baumann J, Huang SF, Gassmann M, Tsao CC, Ogunshola OO. Furin inhibition prevents hypoxic and TGFbeta-mediated blood-brain barrier disruption. Exp Cell Res. 2019;383:111503.","journal-title":"Exp Cell Res"},{"key":"1194_CR28","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1593\/neo.08166","volume":"10","author":"JM Coppola","year":"2008","unstructured":"Coppola JM, Bhojani MS, Ross BD, Rehemtulla A. A small-molecule furin inhibitor inhibits cancer cell motility and invasiveness. Neoplasia. 2008;10:363\u201370.","journal-title":"Neoplasia."},{"key":"1194_CR29","doi-asserted-by":"publisher","first-page":"175883591877829","DOI":"10.1177\/1758835918778297","volume":"10","author":"N Elster","year":"2018","unstructured":"Elster N, Toomey S, Fan Y, Cremona M, Morgan C, Weiner Gorzel K, et al. Frequency, impact and a preclinical study of novel ERBB gene family mutations in HER2-positive breast cancer. Ther Adv Med Oncol. 2018;10:1758835918778297.","journal-title":"Ther Adv Med Oncol"},{"key":"1194_CR30","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S0092-8674(00)81469-5","volume":"94","author":"A Weiss","year":"1998","unstructured":"Weiss A, Schlessinger J. Switching signals on or off by receptor dimerization. Cell. 1998;94:277\u201380.","journal-title":"Cell."},{"key":"1194_CR31","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/372746a0","volume":"372","author":"SR Hubbard","year":"1994","unstructured":"Hubbard SR, Wei L, Ellis L, Hendrickson WA. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature. 1994;372:746\u201354.","journal-title":"Nature."},{"key":"1194_CR32","doi-asserted-by":"publisher","first-page":"5889","DOI":"10.1073\/pnas.90.13.5889","volume":"90","author":"J Blenis","year":"1993","unstructured":"Blenis J. Signal transduction via the MAP kinases: proceed at your own RSK. Proc Natl Acad Sci USA. 1993;90:5889\u201392.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1194_CR33","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/0092-8674(92)90504-6","volume":"71","author":"T Pawson","year":"1992","unstructured":"Pawson T, Gish GD. SH2 and SH3 domains: from structure to function. Cell. 1992;71:359\u201362.","journal-title":"Cell."},{"key":"1194_CR34","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.oraloncology.2015.11.022","volume":"56","author":"JL Geiger","year":"2016","unstructured":"Geiger JL, Grandis JR, Bauman JE. The STAT3 pathway as a therapeutic target in head and neck cancer: barriers and innovations. Oral Oncol. 2016;56:84\u201392.","journal-title":"Oral Oncol."},{"key":"1194_CR35","first-page":"136","volume":"1845","author":"KS Siveen","year":"2014","unstructured":"Siveen KS, Sikka S, Surana R, Dai X, Zhang J, Kumar AP, et al. Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochim Biophys Acta. 2014;1845:136\u201354.","journal-title":"Biochim Biophys Acta"},{"key":"1194_CR36","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1021\/acschembio.5b00945","volume":"11","author":"SL Furtek","year":"2016","unstructured":"Furtek SL, Backos DS, Matheson CJ, Reigan P. Strategies and approaches of targeting STAT3 for cancer treatment. ACS Chem Biol. 2016;11:308\u201318.","journal-title":"ACS Chem Biol"},{"key":"1194_CR37","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.ccell.2015.09.008","volume":"28","author":"S Pradeep","year":"2015","unstructured":"Pradeep S, Huang J, Mora EM, Nick AM, Cho MS, Wu SY, et al. Erythropoietin stimulates tumor growth via EphB4. Cancer Cell. 2015;28:610\u201322.","journal-title":"Cancer Cell."},{"key":"1194_CR38","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.celrep.2016.04.034","volume":"15","author":"P Chaluvally-Raghavan","year":"2016","unstructured":"Chaluvally-Raghavan P, Jeong KJ, Pradeep S, Silva AM, Yu S, Liu W, et al. Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer. Cell Rep. 2016;15:1493\u2013504.","journal-title":"Cell Rep."},{"key":"1194_CR39","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s13046-018-0902-4","volume":"37","author":"C Chen","year":"2018","unstructured":"Chen C, Shenoy AK, Padia R, Fang D, Jing Q, Yang P, et al. Suppression of lung cancer progression by isoliquiritigenin through its metabolite 2, 4, 2\u2019, 4\u2019-Tetrahydroxychalcone. J Exp Clin Cancer Res. 2018;37:243.","journal-title":"J Exp Clin Cancer Res"},{"key":"1194_CR40","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.ccell.2014.10.010","volume":"26","author":"P Chaluvally-Raghavan","year":"2014","unstructured":"Chaluvally-Raghavan P, Zhang F, Pradeep S, Hamilton MP, Zhao X, Rupaimoole R, et al. Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers. Cancer Cell. 2014;26:863\u201379.","journal-title":"Cancer Cell."}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41388-020-1194-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41388-020-1194-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41388-020-1194-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:20:09Z","timestamp":1684617609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-020-1194-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,6]]},"references-count":40,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2020,4,2]]}},"alternative-id":["1194"],"URL":"https:\/\/doi.org\/10.1038\/s41388-020-1194-7","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,6]]},"assertion":[{"value":"24 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}