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dc.contributor.authorPértega-Gomes, Nelma
dc.contributor.authorVizcaino, Jose R.
dc.contributor.authorFelisbino, Sergio
dc.contributor.authorWarren, Anne Y.
dc.contributor.authorShaw, Greg
dc.contributor.authorKay, Jonathan
dc.contributor.authorWhitaker, Hayley
dc.contributor.authorLynch, Andy G.
dc.contributor.authorFryer, Lee
dc.contributor.authorNeal, David E.
dc.contributor.authorMassie, Charles E.
dc.identifier.citationPértega-Gomes , N , Vizcaino , J R , Felisbino , S , Warren , A Y , Shaw , G , Kay , J , Whitaker , H , Lynch , A G , Fryer , L , Neal , D E & Massie , C E 2015 , ' Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer ' , Oncotarget , vol. 6 , no. 25 , pp. 21675-21684 .
dc.identifier.otherPURE: 250730858
dc.identifier.otherPURE UUID: 5f43523f-f417-4b9a-b501-1ca9657128c0
dc.identifier.otherScopus: 84940758201
dc.identifier.otherORCID: /0000-0002-7876-7338/work/35946879
dc.descriptionFelisbino 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 Centre.en
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.
dc.rights© 2015, The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectCastrate resistant diseaseen
dc.subjectMalignant phenotypeen
dc.subjectMonocarboxylate transporter 2en
dc.subjectProstate canceren
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.titleEpigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Statisticsen
dc.description.statusPeer revieweden

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