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The T-box transcription factor brachyury behaves as a tumor suppressor in gliomas

2020-05Journal article Restricted access
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dc.contributor.authorPinto, Filipe
dc.contributor.authorCosta, Angela M.
dc.contributor.authorSantos, Gisele C.
dc.contributor.authorMatsushita, Marcus M.
dc.contributor.authorCosta, Sandra
dc.contributor.authorSilva, Viviane A. O.
dc.contributor.authorMiranda-Goncalves, Vera
dc.contributor.authorLopes, Celeste M.
dc.contributor.authorClara, Carlos A.
dc.contributor.authorBecker, Aline P.
dc.contributor.authorNeder, Luciano
dc.contributor.authorHajj, Glaucia N. M.
dc.contributor.authorda Cunha, Isabela W.
dc.contributor.authorJones, Chris
dc.contributor.authorP. Andrade, Raquel
dc.contributor.authorReis, Rui M.
dc.date.accessioned2021-06-24T11:35:44Z
dc.date.available2021-06-24T11:35:44Z
dc.date.issued2020-05
dc.description.abstractThe oncogene brachyury (TBXT) is a T-box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not been investigated previously in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples. Our glioma samples were analyzed for copy number (n = 372), promoter methylation status (n = 170), and mutation status (n = 1569 tissues and n = 52 cell lines) of the brachyury gene. The prognostic impact of brachyury expression was studied in 1524 glioma patient tumors. The functional impact of brachyury on glioma proliferation, viability, and cell death was evaluated both in vitro and in vivo. Brachyury was expressed in the normal brain, and significantly downregulated in glioma tissues. Loss of brachyury was associated with tumor aggressiveness and poor survival in glioma patients. Downregulation of brachyury was not associated with gene deletion, promoter methylation, or inactivating point mutations. Brachyury re-expression in glioma cells was found to decrease glioma tumorigenesis by induction of autophagy. These data strongly suggest that brachyury behaves as a tumor suppressor gene in gliomas by modulating autophagy. It is important to note that brachyury constitutes an independent positive biomarker of patient prognosis. Our findings indicate that the role of brachyury in tumorigenesis may be tissue-dependent and demands additional investigation to guide rational interventions. (c) 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
dc.description.sponsorshipNational Health Service (NHS)
dc.description.sponsorshipICVS
dc.description.sponsorshipBarretos Cancer Hospital
dc.description.sponsorshipPortuguese FCTPortuguese Foundation for Science and Technology [UID/BIM/04773/2013 CBMR 1334]
dc.description.sponsorshipBrazilian FAPESP grant [2012/19590-0]
dc.description.sponsorshipFCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/81369/2011, SFRH/BPD/115730/2016]
dc.description.sponsorshipProject ON.2 SR&TD Integrated Program - Programa Operacional Regional do Norte (ON.2-O Novo Norte) [NORTE-07-0124-FEDER-000017]
dc.description.sponsorshipQuadro de Referencia Estrategico Nacional (QREN)
dc.description.sponsorshipFundo Europeu de Desenvolvimento Regional (FEDER)European Commission
dc.description.sponsorship[PTDC/SAU-TOX/114549/2009 - FCOMP-01-0124-FEDER-016057]
dc.description.sponsorship[PTDC/SAU-ONC/115513/2009 - FCOMP-01-0124-FEDER-015949]
dc.description.sponsorship[PTDC/MED-ONC/31423/2017 - POCI-01-0145-FEDER-031423]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1002/path.5419
dc.identifier.issn0022-3417
dc.identifier.urihttp://hdl.handle.net/10400.1/16523
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWILEY
dc.relationLEARNING FROM THE EMBRYO: UNDERSTANDING EARLY EMBRYONIC T GENE – BRACHYURY - IMPACT IN HUMAN TUMORIGENESIS
dc.subjectAutophagy
dc.subjectBiomarker
dc.subjectBrachyury
dc.subjectEMT
dc.subjectGlioblastoma
dc.subjectGliomas
dc.subjectPrognosis
dc.subjectTBXT
dc.subjectTumor suppressor
dc.subject.otherOncology
dc.titleThe T-box transcription factor brachyury behaves as a tumor suppressor in gliomas
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleLEARNING FROM THE EMBRYO: UNDERSTANDING EARLY EMBRYONIC T GENE – BRACHYURY - IMPACT IN HUMAN TUMORIGENESIS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F81369%2F2011/PT
oaire.citation.endPage99
oaire.citation.issue1
oaire.citation.startPage87
oaire.citation.titleJournal of Pathology
oaire.citation.volume251
oaire.fundingStream5876
person.familyNameAndrade
person.givenNameRaquel
person.identifier.ciencia-id2312-360B-227A
person.identifier.orcid0000-0002-0397-5917
person.identifier.scopus-author-id7103114918
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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relation.isProjectOfPublicatione13142f2-37b8-4b5a-b2cd-352e62003184
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