{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:22:11Z","timestamp":1793733731694,"version":"4.6.1"},"reference-count":46,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173219"],"award-info":[{"award-number":["82173219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303266"],"award-info":[{"award-number":["82303266"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.isci.2025.113060","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T11:20:32Z","timestamp":1751714432000},"page":"113060","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["TFAP2A enhances tumor stemness and promotes metastasis in pancreatic ductal adenocarcinoma"],"prefix":"10.1016","volume":"28","author":[{"given":"Jiaxin","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zezhi","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minmin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-6972","authenticated-orcid":false,"given":"Lingxi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2025.113060_bib1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1056\/NEJMra1404198","article-title":"Pancreatic adenocarcinoma","volume":"371","author":"Ryan","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.isci.2025.113060_bib2","first-page":"7","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.isci.2025.113060_bib3","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.isci.2025.113060_bib4","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clinicians"},{"key":"10.1016\/j.isci.2025.113060_bib5","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0140-6736(10)62307-0","article-title":"Pancreatic cancer","volume":"378","author":"Vincent","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.isci.2025.113060_bib6","first-page":"316","article-title":"Pancreatic neoplasm in 2011: an update","volume":"12","author":"Saif","year":"2011","journal-title":"J. Pancreas"},{"key":"10.1016\/j.isci.2025.113060_bib7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nrgastro.2016.71","article-title":"Pancreatic cancer: Infiltrating macrophages support liver metastasis","volume":"13","author":"Thomas","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.isci.2025.113060_bib8","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ccr.2013.09.007","article-title":"Origins of metastatic traits","volume":"24","author":"Vanharanta","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2025.113060_bib9","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nrc2622","article-title":"Metastasis: from dissemination to organ-specific colonization","volume":"9","author":"Nguyen","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2025.113060_bib10","first-page":"98","article-title":"The distribution of secondary growths in cancer of the breast. 1889","volume":"8","author":"Paget","year":"1989","journal-title":"Cancer Metastasis Rev."},{"key":"10.1016\/j.isci.2025.113060_bib11","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrc1098","article-title":"The pathogenesis of cancer metastasis: the \u2018seed and soil' hypothesis revisited","volume":"3","author":"Fidler","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2025.113060_bib12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature07829","article-title":"Histone modifications at human enhancers reflect global cell-type-specific gene expression","volume":"459","author":"Heintzman","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.113060_bib13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrm3949","article-title":"The selection and function of cell type-specific enhancers","volume":"16","author":"Heinz","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.113060_bib14","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2014.11.023","article-title":"Environment drives selection and function of enhancers controlling tissue-specific macrophage identities","volume":"159","author":"Gosselin","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.113060_bib15","doi-asserted-by":"crossref","unstructured":"Zorn AM. Liver Development. StemBook. Cambridge, MA: Harvard Stem Cell Institute Copyright: \u00a9 2008 Aaron M. Zorn.; 2008.","DOI":"10.3824\/stembook.1.25.1"},{"key":"10.1016\/j.isci.2025.113060_bib16","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1210\/en.2004-1576","article-title":"Minireview: transcriptional regulation in pancreatic development","volume":"146","author":"Habener","year":"2005","journal-title":"Endocrinology"},{"key":"10.1016\/j.isci.2025.113060_bib17","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/nature03649","article-title":"The initiation of liver development is dependent on Foxa transcription factors","volume":"435","author":"Lee","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.isci.2025.113060_bib18","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1126\/science.1089769","article-title":"Control of pancreas and liver gene expression by HNF transcription factors","volume":"303","author":"Odom","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.isci.2025.113060_bib19","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1038\/sj.emboj.7601883","article-title":"Cited2, a coactivator of HNF4alpha, is essential for liver development","volume":"26","author":"Qu","year":"2007","journal-title":"EMBO J."},{"key":"10.1016\/j.isci.2025.113060_bib20","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1128\/MCB.21.15.5122-5131.2001","article-title":"Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta1-integrin to promote normal liver development","volume":"21","author":"Weinstein","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.113060_bib21","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1053\/j.gastro.2007.08.036","article-title":"Wnt\/beta-catenin signaling in murine hepatic transit amplifying progenitor cells","volume":"133","author":"Hu","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1016\/j.isci.2025.113060_bib22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41422-019-0259-z","article-title":"Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer","volume":"30","author":"Teng","year":"2020","journal-title":"Cell Res."},{"key":"10.1016\/j.isci.2025.113060_bib23","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cell.2017.07.007","article-title":"Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis","volume":"170","author":"Roe","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.isci.2025.113060_bib24","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1136\/gutjnl-2020-321316","article-title":"Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4\u03b1 and SIX1\/4","volume":"70","author":"Camolotto","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.isci.2025.113060_bib25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12943-024-02003-0","article-title":"Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications","volume":"23","author":"Park","year":"2024","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.isci.2025.113060_bib26","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.18632\/aging.202264","article-title":"Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition","volume":"13","author":"Xiong","year":"2021","journal-title":"Aging"},{"key":"10.1016\/j.isci.2025.113060_bib27","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1073\/pnas.1912146117","article-title":"A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.113060_bib28","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/s41467-021-21828-7","article-title":"RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-\u03b22","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2025.113060_bib29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s13046-022-02424-z","article-title":"PITX2C increases the stemness features of hepatocellular carcinoma cells by up-regulating key developmental factors in liver progenitor","volume":"41","author":"Jiang","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.isci.2025.113060_bib30","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/ncb3340","article-title":"Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis","volume":"18","author":"Nielsen","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2025.113060_bib31","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.isci.2025.113060_bib32","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/stem.1022","article-title":"Activin and BMP4 synergistically promote formation of definitive endoderm in human embryonic stem cells","volume":"30","author":"Teo","year":"2012","journal-title":"Stem Cells"},{"key":"10.1016\/j.isci.2025.113060_bib33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gendis.2014.07.005","article-title":"Bone Morphogenetic Protein (BMP) signaling in development and human diseases","volume":"1","author":"Wang","year":"2014","journal-title":"Genes Dis."},{"key":"10.1016\/j.isci.2025.113060_bib34","doi-asserted-by":"crossref","first-page":"E9579","DOI":"10.1073\/pnas.1708341114","article-title":"GATA2\/3-TFAP2A\/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency","volume":"114","author":"Krendl","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2025.113060_bib35","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1136\/gutjnl-2021-326070","article-title":"Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment","volume":"72","author":"Wang","year":"2023","journal-title":"Gut"},{"key":"10.1016\/j.isci.2025.113060_bib36","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1126\/science.aax0249","article-title":"Single-cell transcriptional diversity is a hallmark of developmental potential","volume":"367","author":"Gulati","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.isci.2025.113060_bib37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1080\/15384047.2021.2017223","article-title":"Target c-Myc to treat pancreatic cancer","volume":"23","author":"Ala","year":"2022","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.isci.2025.113060_bib38","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41419-018-0348-9","article-title":"PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis","volume":"9","author":"Zhao","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.isci.2025.113060_bib39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2025.113060_bib40","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1158\/2159-8290.CD-20-1826","article-title":"MYC Levels Regulate Metastatic Heterogeneity in Pancreatic Adenocarcinoma","volume":"12","author":"Maddipati","year":"2022","journal-title":"Cancer Discov."},{"key":"10.1016\/j.isci.2025.113060_bib41","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.7150\/ijbs.34076","article-title":"TFAP2A Induced KRT16 as an Oncogene in Lung Adenocarcinoma via EMT","volume":"15","author":"Yuanhua","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.isci.2025.113060_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2024.101051","article-title":"Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer","volume":"73","author":"Zou","year":"2024","journal-title":"Drug Resist. Updat."},{"key":"10.1016\/j.isci.2025.113060_bib43","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1038\/s41388-018-0220-5","article-title":"Zinc-finger protein 471 suppresses gastric cancer through transcriptionally repressing downstream oncogenic PLS3 and TFAP2A","volume":"37","author":"Cao","year":"2018","journal-title":"Oncogene"},{"key":"10.1016\/j.isci.2025.113060_bib44","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1124\/jpet.114.221358","article-title":"Pharmacological characterization of AZD5069, a slowly reversible CXC chemokine receptor 2 antagonist","volume":"353","author":"Nicholls","year":"2015","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.isci.2025.113060_bib45","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13058-018-0960-8","article-title":"A novel neuregulin - jagged1 paracrine loop in breast cancer transendothelial migration","volume":"20","author":"Cabrera","year":"2018","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.isci.2025.113060_bib46","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2005329","article-title":"Invasive breast carcinoma cells from patients exhibit MenaINV- and macrophage-dependent transendothelial migration","volume":"7","author":"Pignatelli","year":"2014","journal-title":"Sci. Signal."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225013215?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004225013215?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T02:05:45Z","timestamp":1771380345000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004225013215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["S2589004225013215"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2025.113060","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TFAP2A enhances tumor stemness and promotes metastasis in pancreatic ductal adenocarcinoma","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2025.113060","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"113060"}}