{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:21:37Z","timestamp":1790234497814,"version":"4.1.0"},"reference-count":34,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":3146,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["li.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Laboratory Investigation"],"published-print":{"date-parts":[[2014,6]]},"DOI":"10.1038\/labinvest.2014.53","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T08:41:20Z","timestamp":1396860080000},"page":"683-691","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":71,"title":["Upregulated SMAD3 promotes epithelial\u2013mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma"],"prefix":"10.1016","volume":"94","author":[{"given":"Ken","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Masugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Effendi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanako","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyoshi","family":"Hiraoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Kitago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shinoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Itano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiie","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/labinvest.2014.53_bib1","first-page":"69","article-title":"Global cancer statistics","volume":"61","author":"Jemal","year":"2011","journal-title":"CA Cancer J Clin"},{"key":"10.1038\/labinvest.2014.53_bib2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1097\/00000658-199004000-00011","article-title":"Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality","volume":"211","author":"Trede","year":"1990","journal-title":"Ann Surg"},{"key":"10.1038\/labinvest.2014.53_bib3","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1097\/00000658-199506000-00011","article-title":"Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients","volume":"221","author":"Yeo","year":"1995","journal-title":"Ann Surg"},{"key":"10.1038\/labinvest.2014.53_bib4","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/(SICI)1096-9896(200006)191:2<154::AID-PATH603>3.0.CO;2-C","article-title":"The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation","volume":"191","author":"L\u00fcttges","year":"2000","journal-title":"J Pathol"},{"key":"10.1038\/labinvest.2014.53_bib5","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.humpath.2010.01.016","article-title":"Solitary cell infiltration is a novel indicator of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer","volume":"41","author":"Masugi","year":"2010","journal-title":"Hum Pathol"},{"key":"10.1038\/labinvest.2014.53_bib6","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nrc822","article-title":"Epithelial-mesenchymal transitions in tumor progression","volume":"2","author":"Thiery","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"10.1038\/labinvest.2014.53_bib7","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"10.1038\/labinvest.2014.53_bib8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrm1835","article-title":"Complex networks orchestrate epithelial-mesenchymal transitions","volume":"7","author":"Thiery","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1038\/labinvest.2014.53_bib9","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/0016-5085(93)91084-U","article-title":"Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival","volume":"105","author":"Friess","year":"1993","journal-title":"Gastroenterology"},{"key":"10.1038\/labinvest.2014.53_bib10","first-page":"4115","article-title":"The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma","volume":"7","author":"Tascilar","year":"2001","journal-title":"Clin Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib11","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/sj.onc.1206128","article-title":"TGF-beta-induced nuclear localization of Smad2 and Smad3 in Smad4 null cancer cell lines","volume":"22","author":"Fink","year":"2003","journal-title":"Oncogene"},{"key":"10.1038\/labinvest.2014.53_bib12","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1158\/1078-0432.CCR-09-0227","article-title":"SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer","volume":"15","author":"Blackford","year":"2009","journal-title":"Clin Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib13","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1200\/JCO.2003.06.179","article-title":"Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to e-cadherin expression","volume":"21","author":"Shimamura","year":"2003","journal-title":"J Clin Oncol"},{"key":"10.1038\/labinvest.2014.53_bib14","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/labinvest.2009.5","article-title":"Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility","volume":"89","author":"Yamazaki","year":"2009","journal-title":"Lab Invest"},{"key":"10.1038\/labinvest.2014.53_bib15","series-title":"World Health Organization Classification of Tumors of the Digestive System","first-page":"279","article-title":"Tumors of the pancreas","author":"Hruban","year":"2010"},{"key":"10.1038\/labinvest.2014.53_bib16","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1111\/j.1349-7006.2010.01571.x","article-title":"Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer","volume":"101","author":"Uchida","year":"2010","journal-title":"Cancer Sci"},{"key":"10.1038\/labinvest.2014.53_bib17","first-page":"2527","article-title":"DPC4 gene in various tumor types","volume":"56","author":"Schutte","year":"1996","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib18","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1007\/s004280100474","article-title":"Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4\/Smad4","volume":"439","author":"Moore","year":"2001","journal-title":"Virchows Arch"},{"key":"10.1038\/labinvest.2014.53_bib19","doi-asserted-by":"crossref","first-page":"7678","DOI":"10.1073\/pnas.87.19.7678","article-title":"Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential","volume":"87","author":"Welch","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/labinvest.2014.53_bib20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/1359-6101(96)00001-9","article-title":"Tumor suppressor activity of the TGF-beta pathway in human cancers","volume":"7","author":"Markowitz","year":"1996","journal-title":"Cytokine Growth Factor Rev"},{"key":"10.1038\/labinvest.2014.53_bib21","first-page":"4222","article-title":"Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation","volume":"61","author":"Ellenrieder","year":"2001","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib22","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1093\/carcin\/bgl078","article-title":"Smad-Sp1 complexes mediate TGFbeta-induced early transcription of oncogenic Smad7 in pancreatic cancer cells","volume":"27","author":"Jungert","year":"2006","journal-title":"Carcinogenesis"},{"key":"10.1038\/labinvest.2014.53_bib23","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1053\/j.gastro.2011.07.048","article-title":"Transforming growth factor-\u03b2 in the gastrointestinal and hepatic tumor microenvironment","volume":"141","author":"Achyut","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1038\/labinvest.2014.53_bib24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1158\/1078-0432.CCR-06-1467","article-title":"Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression","volume":"13","author":"Wang","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0002-9440(10)64703-7","article-title":"Immunohistochemical labeling for dpc4 mirrors genetic status in pancreatic adenocarcinomas: a new marker of DPC4 inactivation","volume":"156","author":"Wilentz","year":"2000","journal-title":"Am J Pathol"},{"key":"10.1038\/labinvest.2014.53_bib26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000101313","article-title":"Smad4-independent TGF-beta signaling in tumor cell migration","volume":"185","author":"Giehl","year":"2007","journal-title":"Cells Tissues Organs"},{"key":"10.1038\/labinvest.2014.53_bib27","doi-asserted-by":"crossref","first-page":"8108","DOI":"10.1128\/MCB.25.18.8108-8125.2005","article-title":"Smad4 dependency defines two classes of transforming growth factor \u03b2 (TGF-\u03b2) target genes and distinguishes TGF-\u03b2-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses","volume":"25","author":"Levy","year":"2005","journal-title":"Mol Cell Biol"},{"key":"10.1038\/labinvest.2014.53_bib28","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.1158\/0008-5472.CAN-07-5123","article-title":"Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor \u03b2-mediated invasion and metastasis in pancreatic cancer cells","volume":"68","author":"Zhao","year":"2008","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib29","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1158\/1078-0432.CCR-07-1078","article-title":"Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice","volume":"13","author":"Lu","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1038\/labinvest.2014.53_bib30","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1245\/s10434-007-9540-3","article-title":"Epithelial-mesenchymal transition (EMT) and activated extracellular signal-regulated kinase (p-Erk) in surgically resected pancreatic cancer","volume":"14","author":"Javle","year":"2007","journal-title":"Ann Surg Oncol"},{"key":"10.1038\/labinvest.2014.53_bib31","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrc2620","article-title":"Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits","volume":"9","author":"Polyak","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"10.1038\/labinvest.2014.53_bib32","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.biocel.2013.02.017","article-title":"NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL\/SMAD3 signaling pathway","volume":"45","author":"Sun","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"key":"10.1038\/labinvest.2014.53_bib33","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/stem.666","article-title":"Activin\/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors","volume":"29","author":"Brown","year":"2011","journal-title":"Stem Cells"},{"key":"10.1038\/labinvest.2014.53_bib34","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.stem.2012.01.014","article-title":"Signaling network crosstalk in human pluripotent cells: a Smad2\/3-regulated switch that controls the balance between self-renewal and differentiation","volume":"10","author":"Singh","year":"2012","journal-title":"Cell Stem Cell"}],"container-title":["Laboratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/labinvest201453.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/labinvest201453","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722023698?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722023698?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/labinvest201453.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T19:47:47Z","timestamp":1758397667000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0023683722023698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["S0023683722023698"],"URL":"https:\/\/doi.org\/10.1038\/labinvest.2014.53","relation":{},"ISSN":["0023-6837"],"issn-type":[{"value":"0023-6837","type":"print"}],"subject":[],"published":{"date-parts":[[2014,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Upregulated SMAD3 promotes epithelial\u2013mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma","name":"articletitle","label":"Article Title"},{"value":"Laboratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/labinvest.2014.53","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2014 United States & Canadian Academy of Pathology.","name":"copyright","label":"Copyright"}]}}