dc.contributor.author | Reynolds, John | en |
dc.contributor.author | O'Sullivan, Jacintha | en |
dc.contributor.author | Lynam-Lennon, Niamh | en |
dc.date.accessioned | 2015-03-04T14:51:41Z | |
dc.date.available | 2015-03-04T14:51:41Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.citation | Lynam-Lennon N, Maher SG, Maguire A, Phelan J, Muldoon C, Reynolds JV, 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.issn | 1932-6203 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/73413 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Neoadjuvant 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.description.sponsorship | This work was supported by the Health Research Board (http://www.hrb.ie), HRA_POR/2011/63 to S.G.M. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript | en |
dc.format.extent | e100738 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | PloS one | en |
dc.relation.ispartofseries | 9 | en |
dc.relation.ispartofseries | 6 | en |
dc.rights | Y | en |
dc.subject | Neoadjuvant chemoradiation therapy (CRT) | en |
dc.subject.lcsh | Neoadjuvant chemoradiation therapy (CRT) | en |
dc.title | Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/osullij4 | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/reynoljv | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/lynamln | en |
dc.identifier.rssinternalid | 100426 | en |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0100738 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Cancer | en |
dc.subject.TCDTag | Chemoradiation Therapy | en |
dc.subject.TCDTag | Gastrointestinal cancer | en |
dc.subject.TCDTag | Metabolism | en |
dc.subject.TCDTag | Mitochondrial function | en |
dc.subject.TCDTag | NEOADJUVANT THERAPY | en |