TWIST1 Is a Molecular Marker for a Poor Prognosis in Oral Cancer and Represents a Potential Therapeutic Target

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dc.contributor.authorSilva, Sabrina Daniela da
dc.contributor.authorAlaoui-Jamali, Moulay A.
dc.contributor.authorSoares, Fernando Augusto
dc.contributor.authorCarraro, Dirce Maria
dc.contributor.authorBrentani, Helena Paula
dc.contributor.authorHier, Michael
dc.contributor.authorRogatto, Silvia Regina [UNESP]
dc.contributor.authorKowalski, Luiz Paulo
dc.contributor.institutionAC Camargo Canc Ctr
dc.contributor.institutionMcGill Univ
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-12-03T13:07:03Z
dc.date.available2014-12-03T13:07:03Z
dc.date.issued2014-02-01
dc.description.abstractBACKGROUND: Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.METHODSThe expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.RESULTSAmong deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.CONCLUSIONSThe current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC. Cancer 2014;120:352-362. (c) 2013 American Cancer Society.en
dc.description.affiliationAC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo, Brazil
dc.description.affiliationMcGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
dc.description.affiliationMcGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada
dc.description.affiliationMcGill Univ, Dept Otolaryngol Head & Neck Surg, Montreal, PQ H3T 1E2, Canada
dc.description.affiliationUniv Sao Paulo, AC Camargo Canc Ctr, Dept Anat Pathol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Dent, Sao Paulo, Brazil
dc.description.affiliationAC Camargo Canc Ctr, Mol Biol Lab, Sao Paulo, Brazil
dc.description.affiliationAC Camargo Canc Ctr, Biotechnol Lab, Sao Paulo, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Urol, NeoGene Lab, Sao Paulo, Brazil
dc.description.affiliationAC Camargo Canc Ctr, Sao Paulo, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Urol, NeoGene Lab, Sao Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCanadian Institutes for Health Research (CIHR)
dc.description.sponsorshipCanadian Cancer Society
dc.description.sponsorshipQuebec Breast Cancer Foundation
dc.format.extent352-362
dc.identifierhttp://dx.doi.org/10.1002/cncr.28404
dc.identifier.citationCancer. Hoboken: Wiley-blackwell, v. 120, n. 3, p. 352-362, 2014.
dc.identifier.doi10.1002/cncr.28404
dc.identifier.issn0008-543X
dc.identifier.lattes2259986546265579
dc.identifier.urihttp://hdl.handle.net/11449/111203
dc.identifier.wosWOS:000330267700008
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofCancer
dc.relation.ispartofjcr6.537
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectoral squamous cell carcinomaen
dc.subjectepithelial-mesenchymal transitionen
dc.subjectTwisten
dc.subjectmetastasisen
dc.subjectclinical outcomeen
dc.titleTWIST1 Is a Molecular Marker for a Poor Prognosis in Oral Cancer and Represents a Potential Therapeutic Targeten
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-Blackwell
unesp.author.lattes2259986546265579
unesp.author.orcid0000-0003-1647-7842[3]
unesp.author.orcid0000-0001-5667-1418[4]
unesp.author.orcid0000-0001-5865-9308[8]
unesp.author.orcid0000-0001-5192-4682[5]
unesp.author.orcid0000-0002-0481-156X[8]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatupt

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