dc.contributor.author | van Weverwijk, A | |
dc.contributor.author | Koundouros, N | |
dc.contributor.author | Iravani, M | |
dc.contributor.author | Ashenden, M | |
dc.contributor.author | Gao, Q | |
dc.contributor.author | Poulogiannis, G | |
dc.contributor.author | Jungwirth, U | |
dc.contributor.author | Isacke, CM | |
dc.date.accessioned | 2019-06-19T15:04:41Z | |
dc.date.issued | 2019-06-20 | |
dc.identifier.citation | Nature communications, 2019, 10 (1), pp. 2698 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3258 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-019-10592-4 | |
dc.description.abstract | The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability in disseminated disease. We identify the aldo-keto reductase AKR1B10 as a metastasis enhancer that has little impact on primary tumour growth or dissemination but promotes effective tumour growth in secondary sites and, in human disease, is associated with an increased risk of distant metastatic relapse. AKR1B10High tumour cells have reduced glycolytic capacity and dependency on glucose as fuel source but increased utilisation of fatty acid oxidation. Conversely, in both 3D tumour spheroid assays and in vivo metastasis assays, inhibition of fatty acid oxidation blocks AKR1B10High-enhanced metastatic colonisation with no impact on AKR1B10Low cells. Finally, mechanistic analysis supports a model in which AKR1B10 serves to limit the toxic side effects of oxidative stress thereby sustaining fatty acid oxidation in metabolically challenging metastatic environments. | |
dc.format | Electronic | |
dc.format.extent | 2698 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Spheroids, Cellular | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Breast Neoplasms | |
dc.subject | Lung Neoplasms | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Aldehyde Reductase | |
dc.subject | Fatty Acids | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Oxidation-Reduction | |
dc.subject | Glycolysis | |
dc.subject | Oxidative Stress | |
dc.subject | Female | |
dc.subject | HEK293 Cells | |
dc.subject | Aldo-Keto Reductases | |
dc.title | Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-05-16 | |
rioxxterms.versionofrecord | 10.1038/s41467-019-10592-4 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-06-20 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism | |
pubs.publication-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Signalling & Cancer Metabolism | |
dc.contributor.icrauthor | Koundouros, Nikolaos | |
dc.contributor.icrauthor | Iravani, Marjan | |
dc.contributor.icrauthor | Gao, Qiong | |
dc.contributor.icrauthor | Poulogiannis, Georgios | |
dc.contributor.icrauthor | Isacke, Clare | |