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dc.contributor.authorConnon, Stephenen
dc.contributor.authorReynolds, Johnen
dc.contributor.authorLynam-Lennon, Niamhen
dc.contributor.authorPhelan, Jamesen
dc.contributor.authorMaher, Stephenen
dc.date.accessioned2014-10-22T14:43:42Z
dc.date.available2014-10-22T14:43:42Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationLynam-Lennon, N., Maher, S.G., Maguire, A., (...), Reynolds, J.V., O'Sullivan, J., Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma, PLoS ONE, 9, 6, 2014, e100738-en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/71699
dc.descriptionPUBLISHEDen
dc.description.abstractNeoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R) demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC.en
dc.format.extente100738en
dc.language.isoenen
dc.relation.ispartofseriesPLoS ONEen
dc.relation.ispartofseries9en
dc.relation.ispartofseries6en
dc.rightsYen
dc.subjectOxidative phosphorylationen
dc.subjectMitochondriaen
dc.subjectGlycolysisen
dc.subjectEpitheliumen
dc.subjectEnergy metabolismen
dc.subjectCell metabolismen
dc.subjectCancer treatmenten
dc.subjectBiopsyen
dc.titleAltered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinomaen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/connonsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mahersten
dc.identifier.peoplefinderurlhttp://people.tcd.ie/phelanj3en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/reynoljven
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lynamlnen
dc.identifier.rssinternalid95367en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0100738en
dc.rights.ecaccessrightsopenAccess
dc.identifier.orcid_id0000-0003-2984-9246en


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