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Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

2015-08-28Journal article Open access
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dc.contributor.authorPertega-Gomes, N.
dc.contributor.authorVizcaino, J.
dc.contributor.authorFelisbino, S.
dc.contributor.authorWarren, A.
dc.contributor.authorShaw, G.
dc.contributor.authorKay, J.
dc.contributor.authorWhitaker, H.
dc.contributor.authorLynch, A.
dc.contributor.authorFryer, L.
dc.contributor.authorNeal, D.
dc.contributor.authorMassie, C.
dc.date.accessioned2016-07-26T13:34:42Z
dc.date.available2016-07-26T13:34:42Z
dc.date.issued2015-08-28
dc.description.abstractMonocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.pt_PT
dc.description.sponsorshipFelisbino S. received a fellowship from the Sao Paulo Research Foundation (FAPESP) ref. 2013/08830-2 and 2013/06802-1. Anne Y Warren research time funded by: Cambridge Biomedical Research Centrept_PT
dc.identifier.citationOncotarget. 2015 Aug 28;6(25):21675-84pt_PT
dc.identifier.doi10.18632/oncotarget.4328pt_PT
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10400.16/1977
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[]=4328&pubmed-linkout=1pt_PT
dc.subject5' Untranslated Regionspt_PT
dc.subjectAmino Acid Motifspt_PT
dc.subjectCohort Studiespt_PT
dc.subjectHumanspt_PT
dc.subjectImmunohistochemistrypt_PT
dc.subjectMalept_PT
dc.subjectMicroscopy, Confocalpt_PT
dc.subjectMonocarboxylic Acid Transporterspt_PT
dc.subjectNeoplasm Metastasispt_PT
dc.subjectPhenotypept_PT
dc.subjectProstatic Neoplasmspt_PT
dc.subjectProtein Biosynthesispt_PT
dc.subjectRNA, Small Interferingpt_PT
dc.subjectReceptors, Androgenpt_PT
dc.subjectSignal Transductionpt_PT
dc.subjectTrans-Activatorspt_PT
dc.subjectEpigenesis, Geneticpt_PT
dc.subjectGene Expression Regulation, Neoplasticpt_PT
dc.titleEpigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.endPage21684pt_PT
oaire.citation.issue25pt_PT
oaire.citation.startPage21675pt_PT
oaire.citation.titleOncotargetpt_PT
oaire.citation.volume6pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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