{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:44:49Z","timestamp":1789911889637,"version":"4.0.1"},"reference-count":94,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Biol."],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epithelial-to-mesenchymal transition (EMT) is a fundamental developmental process wherein polarized epithelial cells lose their junctional architecture and apical-basal polarity to become motile mesenchymal cells, and there is emerging evidence for its role in propagating tumor dissemination. While many multifaceted nodules converge onto the EMT program, in this review we will highlight the fundamental biology of the signaling schemas that enable EMT. In many cancers, the property of tumor dissemination and metastasis is closely associated with re-enabling developmental properties such as EMT. We discuss the molecular complexity of the tumor heterogeneity in terms of EMT-based gene expression molecular subtypes, and the rewiring of critical signaling nodules in the subtypes displaying higher degrees of EMT can be therapeutically exploited. Specifically in the context of a deadly malignancy such as ovarian cancer where there are no defined mutations or limited biomarkers for developing targeted therapy or personalized medicine, we highlight the importance of identifying EMT-based subtypes that will improve therapeutic intervention. In ovarian cancer, the poor prognosis mesenchymal \u2018Mes\u2019 subtype presents with amplified signaling of the receptor tyrosine kinase (RTK) AXL, extensive crosstalk with other RTKs such as cMET, EGFR and HER2, and sustained temporal activation of extracellular-signal regulated kinase (ERK) leading to induction of EMT transcription factor Slug, underscoring a pathway addiction in Mes that can be therapeutically targeted. We will further examine the emergence of therapeutic modalities in these EMT subtypes and finally conclude with potential interdisciplinary biophysical methodologies to provide additional insights in deciphering the mechanistic and biochemical aspects of EMT.<\/jats:p>\n                  <jats:p>This review intends to provide an overview of the cellular and molecular changes accompanying epithelial-to-mesenchymal transition (EMT) in development and the requisition of this evolutionarily conserved pathway in cancer progression and metastatic disease. Specifically, in a heterogeneous disease such as ovarian cancer lacking defined targetable mutations, the identification of EMT-based subtypes has opened avenues to tailor precision personalized medicine. In particular, using the oncogenic RTK AXL as an example, we will highlight how this classification enables EMT-subtype specific identification of targets that could improve treatment options for patients and how there is a growing need for biophysical approaches to model dynamic processes such as EMT.<\/jats:p>","DOI":"10.1088\/1478-3975\/ab157a","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T23:18:52Z","timestamp":1554247132000},"page":"041004","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":59,"title":["Epithelial-to-mesenchymal transition: lessons from development, insights into cancer and the potential of EMT-subtype based therapeutic intervention"],"prefix":"10.1088","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2424-5470","authenticated-orcid":false,"given":"Jane","family":"Antony","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Thiery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby Yun-Ju","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"pbab157abib001","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1146\/annurev.cellbio.18.022602.131838","type":"journal-article","article-title":"Molecular mechanisms of epithelial morphogenesis","volume":"18","author":"Schock","year":"2002","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"pbab157abib002","doi-asserted-by":"publisher","first-page":"5991","DOI":"10.1158\/0008-5472.CAN-05-0616","type":"journal-article","article-title":"Carcinoma invasion and metastasis: a role for epithelial\u2013mesenchymal transition?","volume":"65","author":"Thompson","year":"2005","journal-title":"Cancer Res."},{"key":"pbab157abib003","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ceb.2003.11.001","type":"journal-article","article-title":"Prespecification and plasticity: shifting mechanisms of cell migration","volume":"16","author":"Friedl","year":"2004","journal-title":"Curr. Opin. Cell Biol."},{"key":"pbab157abib004","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/nrc822","type":"journal-article","article-title":"Epithelial\u2013mesenchymal transitions in tumour progression","volume":"2","author":"Thiery","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"pbab157abib005","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1161\/01.RES.0000038961.53759.3C","type":"journal-article","article-title":"Development of the coronary vessel system","volume":"91","author":"Reese","year":"2002","journal-title":"Circ. Res."},{"key":"pbab157abib006","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1083\/jcb.200601018","type":"journal-article","article-title":"The epithelial\u2013mesenchymal transition: new insights in signaling, development, and disease","volume":"172","author":"Lee","year":"2006","journal-title":"J. Cell Biol."},{"key":"pbab157abib007","doi-asserted-by":"publisher","first-page":"3471","DOI":"10.1242\/dev.071209","type":"journal-article","article-title":"Epithelial\u2013mesenchymal transitions: insights from development","volume":"139","author":"Lim","year":"2012","journal-title":"Development"},{"key":"pbab157abib008","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/S0959-437X(00)00218-5","type":"journal-article","article-title":"Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration","volume":"11","author":"Locascio","year":"2001","journal-title":"Curr. Opin. Genet. Dev."},{"key":"pbab157abib009","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1242\/dev.126.18.4129","type":"journal-article","article-title":"Coelom formation: binary decision of the lateral plate mesoderm is controlled by the ectoderm","volume":"126","author":"Funayama","year":"1999","journal-title":"Development"},{"key":"pbab157abib010","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41556-018-0195-z","type":"journal-article","article-title":"Mesenchymal\u2013epithelial transition in development and reprogramming","volume":"21","author":"Pei","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"pbab157abib011","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1387\/ijdb.041794hp","type":"journal-article","article-title":"Transcriptional regulation of cadherins during development and carcinogenesis","volume":"48","author":"Peinado","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"pbab157abib012","doi-asserted-by":"publisher","first-page":"45801","DOI":"10.1074\/jbc.M308168200","type":"journal-article","article-title":"Elevated hyaluronan production induces mesenchymal and transformed properties in epithelial cells","volume":"278","author":"Zoltan-Jones","year":"2003","journal-title":"J. Biol. Chem."},{"key":"pbab157abib013","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nrm3758","type":"journal-article","article-title":"Molecular mechanisms of epithelial\u2013mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"pbab157abib014","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1016\/j.febslet.2012.02.037","type":"journal-article","article-title":"Regulation of EMT by TGFbeta in cancer","volume":"586","author":"Heldin","year":"2012","journal-title":"FEBS Lett."},{"key":"pbab157abib015","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nature03319","type":"journal-article","article-title":"Wnt signalling in stem cells and cancer","volume":"434","author":"Reya","year":"2005","journal-title":"Nature"},{"key":"pbab157abib016","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2174\/138945010791170860","type":"journal-article","article-title":"The role of Notch signaling pathway in epithelial\u2013mesenchymal transition (EMT) during development and tumor aggressiveness","volume":"11","author":"Wang","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"pbab157abib017","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/S1535-6108(03)00304-0","type":"journal-article","article-title":"Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion","volume":"4","author":"Lu","year":"2003","journal-title":"Cancer Cell"},{"key":"pbab157abib018","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/309587","type":"journal-article","article-title":"Differential downregulation of e-cadherin and desmoglein by epidermal growth factor","volume":"2012","author":"Chavez","year":"2012","journal-title":"Dermatol. Res. Pract."},{"key":"pbab157abib019","doi-asserted-by":"publisher","first-page":"13116","DOI":"10.1074\/jbc.271.22.13116","type":"journal-article","article-title":"Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein","volume":"271","author":"Fixman","year":"1996","journal-title":"J. Biol. Chem."},{"key":"pbab157abib020","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.tcb.2009.07.002","type":"journal-article","article-title":"Crosstalk in Met receptor oncogenesis","volume":"19","author":"Lai","year":"2009","journal-title":"Trends Cell Biol."},{"key":"pbab157abib021","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1111\/j.1349-7006.2011.02096.x","type":"journal-article","article-title":"Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma","volume":"102","author":"Susuki","year":"2011","journal-title":"Cancer Sci."},{"key":"pbab157abib022","doi-asserted-by":"publisher","first-page":"4942","DOI":"10.1038\/sj.onc.1204660","type":"journal-article","article-title":"IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition","volume":"20","author":"Morali","year":"2001","journal-title":"Oncogene"},{"key":"pbab157abib023","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1128\/MCB.01315-06","type":"journal-article","article-title":"Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail","volume":"27","author":"Kim","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"pbab157abib024","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1158\/0008-5472.CAN-07-2559","type":"journal-article","article-title":"Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells","volume":"68","author":"Graham","year":"2008","journal-title":"Cancer Res."},{"key":"pbab157abib025","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","type":"journal-article","article-title":"Epithelial\u2013mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"pbab157abib026","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1101\/gad.1653708","type":"journal-article","article-title":"Role of platelet-derived growth factors in physiology and medicine","volume":"22","author":"Andrae","year":"2008","journal-title":"Genes Dev."},{"key":"pbab157abib027","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.cell.2006.08.036","type":"journal-article","article-title":"P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing axin from beta-catenin","volume":"127","author":"Yang","year":"2006","journal-title":"Cell"},{"key":"pbab157abib028","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nrm1911","type":"journal-article","article-title":"VEGF receptor signalling\u2014in control of vascular function","volume":"7","author":"Olsson","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"pbab157abib029","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.yexcr.2009.11.020","type":"journal-article","article-title":"VEGF elicits epithelial\u2013mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop","volume":"316","author":"Gonzalez-Moreno","year":"2010","journal-title":"Exp. Cell Res."},{"key":"pbab157abib030","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1016\/j.yexcr.2008.05.004","type":"journal-article","article-title":"Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression","volume":"314","author":"Wanami","year":"2008","journal-title":"Exp. Cell Res."},{"key":"pbab157abib031","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.devcel.2008.05.009","type":"journal-article","article-title":"Epithelial\u2013mesenchymal transition: at the crossroads of development and tumor metastasis","volume":"14","author":"Yang","year":"2008","journal-title":"Dev. Cell"},{"key":"pbab157abib032","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1101\/gad.225334.113","type":"journal-article","article-title":"Epithelial\u2013mesenchymal plasticity in carcinoma metastasis","volume":"27","author":"Tsai","year":"2013","journal-title":"Genes Dev."},{"key":"pbab157abib033","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","type":"journal-article","article-title":"The basics of epithelial\u2013mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"J. Clin. Invest."},{"key":"pbab157abib034","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1159\/000147748","type":"journal-article","article-title":"An overview of epithelio-mesenchymal transformation","volume":"154","author":"Hay","year":"1995","journal-title":"Acta Anat."},{"key":"pbab157abib035","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","type":"journal-article","article-title":"Emt: 2016","volume":"166","author":"Nieto","year":"2016","journal-title":"Cell"},{"key":"pbab157abib036","doi-asserted-by":"crossref","first-page":"22098","DOI":"10.18632\/oncotarget.4300","type":"journal-article","article-title":"Functional relevance of a six mesenchymal gene signature in epithelial\u2013mesenchymal transition (EMT) reversal by the triple angiokinase inhibitor, nintedanib (BIBF1120)","volume":"6","author":"Huang","year":"2015","journal-title":"Oncotarget"},{"key":"pbab157abib037","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/ncb2548","type":"journal-article","article-title":"Classifying collective cancer cell invasion","volume":"14","author":"Friedl","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"pbab157abib038","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.ccr.2013.03.004","type":"journal-article","article-title":"Tumor dissemination: an EMT affair","volume":"23","author":"Thiery","year":"2013","journal-title":"Cancer Cell"},{"key":"pbab157abib039","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.1228522","type":"journal-article","article-title":"Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition","volume":"339","author":"Yu","year":"2013","journal-title":"Science"},{"key":"pbab157abib040","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/35000025","type":"journal-article","article-title":"The transcription factor Snail controls epithelial\u2013mesenchymal transitions by repressing E-cadherin expression","volume":"2","author":"Cano","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"pbab157abib041","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41586-018-0040-3","type":"journal-article","article-title":"Identification of the tumour transition states occurring during EMT","volume":"556","author":"Pastushenko","year":"2018","journal-title":"Nature"},{"key":"pbab157abib042","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.ejca.2012.06.026","type":"journal-article","article-title":"Resistance to platinum-based chemotherapy is associated with epithelial to mesenchymal transition in epithelial ovarian cancer","volume":"49","author":"Marchini","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"pbab157abib043","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ygyno.2009.05.022","type":"journal-article","article-title":"A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer","volume":"114","author":"Hu","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"pbab157abib044","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1007\/s12672-010-0043-5","type":"journal-article","article-title":"MicroRNAs link estrogen receptor alpha status and Dicer levels in breast cancer","volume":"1","author":"Cochrane","year":"2010","journal-title":"Horm. Cancer"},{"key":"pbab157abib045","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.biopha.2012.06.002","type":"journal-article","article-title":"Review of miR-200b and cancer chemosensitivity","volume":"66","author":"Feng","year":"2012","journal-title":"Biomed. Pharmacother."},{"key":"pbab157abib046","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1158\/1535-7163.MCT-12-0463","type":"journal-article","article-title":"Restoration of miR-200c to ovarian cancer reduces tumor burden and increases sensitivity to paclitaxel","volume":"11","author":"Cittelly","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"pbab157abib047","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1016\/S0140-6736(13)62146-7","type":"journal-article","article-title":"Ovarian cancer","volume":"384","author":"Jayson","year":"2014","journal-title":"Lancet"},{"key":"pbab157abib048","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nrc1611","type":"journal-article","article-title":"Ovarian cancer metastasis: integrating insights from disparate model organisms","volume":"5","author":"Naora","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"pbab157abib049","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0303-7207(03)00068-6","type":"journal-article","article-title":"Cell-cell adhesion in the normal ovary and ovarian tumors of epithelial origin; an exception to the rule","volume":"202","author":"Sundfeldt","year":"2003","journal-title":"Mol. Cell Endocrinol."},{"key":"pbab157abib050","doi-asserted-by":"publisher","first-page":"8319","DOI":"10.1158\/0008-5472.CAN-06-0410","type":"journal-article","article-title":"Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis","volume":"66","author":"Christiansen","year":"2006","journal-title":"Cancer Res."},{"key":"pbab157abib051","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1007\/s00428-006-0274-6","type":"journal-article","article-title":"Expression of E-cadherin transcriptional regulators in ovarian carcinoma","volume":"449","author":"Elloul","year":"2006","journal-title":"Virchows Arch."},{"key":"pbab157abib052","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/jcp.21240","type":"journal-article","article-title":"Epithelial\u2013mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm","volume":"213","author":"Ahmed","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"pbab157abib053","doi-asserted-by":"publisher","first-page":"5198","DOI":"10.1158\/1078-0432.CCR-08-0196","type":"journal-article","article-title":"Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome","volume":"14","author":"Tothill","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"pbab157abib054","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nature10166","type":"journal-article","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","author":"Cancer Genome Atlas Research Network","year":"2011","journal-title":"Nature"},{"key":"pbab157abib055","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1002\/emmm.201201823","type":"journal-article","article-title":"Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer","volume":"5","author":"Tan","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"pbab157abib056","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018064","type":"journal-article","article-title":"Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers","volume":"6","author":"Helland","year":"2011","journal-title":"PLoS One"},{"key":"pbab157abib057","doi-asserted-by":"publisher","first-page":"e1346","DOI":"10.1038\/cddis.2014.302","type":"journal-article","article-title":"FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt\/PCP pathway","volume":"5","author":"Asad","year":"2014","journal-title":"Cell Death Dis."},{"key":"pbab157abib058","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.ccr.2012.12.020","type":"journal-article","article-title":"Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer","volume":"23","author":"Yang","year":"2013","journal-title":"Cancer Cell"},{"key":"pbab157abib059","doi-asserted-by":"publisher","first-page":"19943","DOI":"10.1038\/srep19943","type":"journal-article","article-title":"GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification","volume":"6","author":"Chung","year":"2016","journal-title":"Sci. Rep."},{"key":"pbab157abib060","author":"Yun-Ju Huang","year":"2012","type":"other"},{"key":"pbab157abib061","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.15252\/emmm.201404208","type":"journal-article","article-title":"Epithelial\u2013mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients","volume":"6","author":"Tan","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"pbab157abib062","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/path.4536","type":"journal-article","article-title":"Efficient molecular subtype classification of high-grade serous ovarian cancer","volume":"236","author":"Leong","year":"2015","journal-title":"J. Pathol."},{"key":"pbab157abib063","first-page":"35","type":"journal-article","article-title":"TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer","volume":"vol 100","author":"Linger","year":"2008"},{"key":"pbab157abib064","first-page":"471","type":"journal-article","article-title":"Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts","volume":"12","author":"Goruppi","year":"1996","journal-title":"Oncogene"},{"key":"pbab157abib065","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1073\/pnas.0909333107","type":"journal-article","article-title":"Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival","volume":"107","author":"Gjerdrum","year":"2010","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"pbab157abib066","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1158\/0008-5472.CAN-09-2997","type":"journal-article","article-title":"R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer","volume":"70","author":"Holland","year":"2010","journal-title":"Cancer Res."},{"key":"pbab157abib067","doi-asserted-by":"publisher","first-page":"S467","DOI":"10.1245\/s10434-012-2795-3","type":"journal-article","article-title":"Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients","volume":"20","author":"Ishikawa","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"pbab157abib068","doi-asserted-by":"publisher","first-page":"618","DOI":"10.4161\/cbt.8.7.7923","type":"journal-article","article-title":"The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target","volume":"8","author":"Koorstra","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"pbab157abib069","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1002\/cncr.25483","type":"journal-article","article-title":"Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma","volume":"117","author":"Song","year":"2011","journal-title":"Cancer"},{"key":"pbab157abib070","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/ng.2330","type":"journal-article","article-title":"Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer","volume":"44","author":"Zhang","year":"2012","journal-title":"Nat. Genet."},{"key":"pbab157abib071","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1158\/1078-0432.CCR-12-1558","type":"journal-article","article-title":"An epithelial\u2013mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance","volume":"19","author":"Byers","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"pbab157abib072","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.ccell.2015.03.010","type":"journal-article","article-title":"AXL mediates resistance to PI3Kalpha inhibition by activating the EGFR\/PKC\/mTOR axis in head and neck and esophageal squamous cell carcinomas","volume":"27","author":"Elkabets","year":"2015","journal-title":"Cancer Cell"},{"key":"pbab157abib073","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/nrc3847","type":"journal-article","article-title":"The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer","volume":"14","author":"Graham","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"pbab157abib074","doi-asserted-by":"publisher","first-page":"7570","DOI":"10.1158\/0008-5472.CAN-10-1267","type":"journal-article","article-title":"AXL Is an essential factor and therapeutic target for metastatic ovarian cancer","volume":"70","author":"Rankin","year":"2010","journal-title":"Cancer Res."},{"key":"pbab157abib075","doi-asserted-by":"publisher","first-page":"ra97","DOI":"10.1126\/scisignal.aaf8175","type":"journal-article","article-title":"The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific therapeutic target for ovarian cancer","volume":"9","author":"Antony","year":"2016","journal-title":"Sci. Signal."},{"key":"pbab157abib076","doi-asserted-by":"publisher","first-page":"fs14","DOI":"10.1126\/scisignal.aai7619","type":"journal-article","article-title":"New twists in the AXL(e) of tumor progression","volume":"9","author":"Halmos","year":"2016","journal-title":"Sci. Signal."},{"key":"pbab157abib077","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846492","type":"journal-article","article-title":"Synergistic inactivation of AXL: a (cross)road to cure ovarian cancer?","volume":"19","author":"Zurzolo","year":"2018","journal-title":"EMBO Rep."},{"key":"pbab157abib078","doi-asserted-by":"publisher","first-page":"e1263716","DOI":"10.1080\/23723556.2016.1263716","type":"journal-article","article-title":"Targeting the AXL signaling pathway in ovarian cancer","volume":"4","author":"Huang","year":"2017","journal-title":"Mol. Cell. Oncol."},{"key":"pbab157abib079","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1158\/2159-8290.CD-11-0256","type":"journal-article","article-title":"The OPCML tumor suppressor functions as a cell surface repressor-adaptor, negatively regulating receptor tyrosine kinases in epithelial ovarian cancer","volume":"2","author":"McKie","year":"2012","journal-title":"Cancer Discov."},{"key":"pbab157abib080","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1158\/1535-7163.MCT-17-0081","type":"journal-article","article-title":"The tumor-suppressor protein OPCML potentiates anti-EGFR- and anti-HER2-targeted therapy in HER2-positive ovarian and breast cancer","volume":"16","author":"Zanini","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"pbab157abib081","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201745670","type":"journal-article","article-title":"The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer","volume":"19","author":"Antony","year":"2018","journal-title":"EMBO Rep."},{"key":"pbab157abib082","doi-asserted-by":"publisher","first-page":"3725","DOI":"10.1158\/0008-5472.CAN-17-0392","type":"journal-article","article-title":"AXL-driven EMT state as a targetable conduit in cancer","volume":"77","author":"Antony","year":"2017","journal-title":"Cancer Res."},{"key":"pbab157abib083","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.1158\/0008-5472.CAN-14-1009","type":"journal-article","article-title":"AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs","volume":"74","author":"Wilson","year":"2014","journal-title":"Cancer Res."},{"key":"pbab157abib084","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1158\/2159-8290.CD-13-0520","type":"journal-article","article-title":"Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation","volume":"4","author":"Salt","year":"2014","journal-title":"Cancer Discov."},{"key":"pbab157abib085","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0092-8674(03)00108-9","type":"journal-article","article-title":"Sticky business: orchestrating cellular signals at adherens junctions","volume":"112","author":"Perez-Moreno","year":"2003","journal-title":"Cell"},{"key":"pbab157abib086","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1242\/jcs.00167","type":"journal-article","article-title":"Nectin and afadin: novel organizers of intercellular junctions","volume":"116","author":"Takai","year":"2003","journal-title":"J. Cell Sci."},{"key":"pbab157abib087","doi-asserted-by":"publisher","first-page":"4753","DOI":"10.1074\/jbc.M412544200","type":"journal-article","article-title":"Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and -3","volume":"280","author":"Martinez-Rico","year":"2005","journal-title":"J. Biol. Chem."},{"key":"pbab157abib088","doi-asserted-by":"publisher","first-page":"2901","DOI":"10.1074\/jbc.M506185200","type":"journal-article","article-title":"Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains","volume":"281","author":"Chu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"pbab157abib089","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1083\/jcb.200312013","type":"journal-article","article-title":"Roles played by a subset of integrin signaling molecules in cadherin-based cell-cell adhesion","volume":"166","author":"Yano","year":"2004","journal-title":"J. Cell Biol."},{"key":"pbab157abib090","doi-asserted-by":"publisher","first-page":"19264","DOI":"10.1073\/pnas.0804598105","type":"journal-article","article-title":"A genetically encoded fluorescent sensor of ERK activity","volume":"105","author":"Harvey","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"pbab157abib091","doi-asserted-by":"publisher","first-page":"4647","DOI":"10.1091\/mbc.e11-01-0072","type":"journal-article","article-title":"Development of an optimized backbone of FRET biosensors for kinases and GTPases","volume":"22","author":"Komatsu","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"pbab157abib092","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064029","type":"journal-article","article-title":"Intravital FRET imaging of tumor cell viability and mitosis during chemotherapy","volume":"8","author":"Janssen","year":"2013","journal-title":"PLoS One"},{"key":"pbab157abib093","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.4161\/cc.10.17.17188","type":"journal-article","article-title":"Tracking the intermediate stages of epithelial\u2013mesenchymal transition in epithelial stem cells and cancer","volume":"10","author":"Jordan","year":"2011","journal-title":"Cell Cycle"},{"key":"pbab157abib094","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ccr.2012.09.022","type":"journal-article","article-title":"Spatiotemporal regulation of epithelial\u2013mesenchymal transition is essential for squamous cell carcinoma metastasis","volume":"22","author":"Tsai","year":"2012","journal-title":"Cancer Cell"}],"container-title":["Physical Biology"],"original-title":[],"link":[{"URL":"http:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"http:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a","content-type":"text\/html","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:26:27Z","timestamp":1773491187000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1478-3975\/ab157a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,7]]},"references-count":94,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,5,7]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1478-3975\/ab157a","relation":{},"ISSN":["1478-3967","1478-3975"],"issn-type":[{"value":"1478-3967","type":"print"},{"value":"1478-3975","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,7]]},"assertion":[{"value":"Epithelial-to-mesenchymal transition: lessons from development, insights into cancer and the potential of EMT-subtype based therapeutic intervention","name":"article_title","label":"Article Title"},{"value":"Physical Biology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2019 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2018-10-31","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2019-04-02","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2019-05-07","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}