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Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

dc.contributor.authorPinto, F.ilipe
dc.contributor.authorPértega-Gomes, N.
dc.contributor.authorVizcaíno, J.
dc.contributor.authorAndrade, R.
dc.contributor.authorCárcano, F.
dc.contributor.authorReis, R.
dc.date.accessioned2017-07-11T10:25:26Z
dc.date.available2017-07-11T10:25:26Z
dc.date.issued2016-05-17
dc.description.abstractProstate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationOncotarget. 2016 May 17;7(20):28891-902pt_PT
dc.identifier.doi10.18632/oncotarget.8499pt_PT
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10400.16/2143
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherImpact Journalspt_PT
dc.relation.publisherversionhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8499&pubmed-linkout=1pt_PT
dc.titleBrachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.endPage28902pt_PT
oaire.citation.issue20pt_PT
oaire.citation.startPage28891pt_PT
oaire.citation.titleOncotargetpt_PT
oaire.citation.volume7pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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