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dc.contributor.authorvan Weverwijk, Aen_US
dc.contributor.authorKoundouros, Nen_US
dc.contributor.authorIravani, Men_US
dc.contributor.authorAshenden, Men_US
dc.contributor.authorGao, Qen_US
dc.contributor.authorPoulogiannis, Gen_US
dc.contributor.authorJungwirth, Uen_US
dc.contributor.authorIsacke, CMen_US
dc.date.accessioned2019-06-19T15:04:41Z
dc.date.issued2019-06-20en_US
dc.identifier.citationNature communications, 2019, 10 (1), pp. 2698 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3258
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-019-10592-4en_US
dc.description.abstractThe 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.en_US
dc.formatElectronicen_US
dc.format.extent2698 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectCell Line, Tumoren_US
dc.subjectSpheroids, Cellularen_US
dc.subjectAnimalsen_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectLung Neoplasmsen_US
dc.subjectNeoplasm Recurrence, Localen_US
dc.subjectAldehyde Reductaseen_US
dc.subjectFatty Acidsen_US
dc.subjectXenograft Model Antitumor Assaysen_US
dc.subjectOxidation-Reductionen_US
dc.subjectGlycolysisen_US
dc.subjectOxidative Stressen_US
dc.subjectFemaleen_US
dc.subjectHEK293 Cellsen_US
dc.titleMetabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-16en_US
rioxxterms.versionofrecord10.1038/s41467-019-10592-4en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-06-20en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
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-statusPublisheden_US
pubs.volume10en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Cell Biologyen_US
icr.researchteamSignalling & Cancer Metabolismen_US
dc.contributor.icrauthorIsacke, Clareen_US
dc.contributor.icrauthorIravani, Marjanen_US
dc.contributor.icrauthorGao, Qiongen_US
dc.contributor.icrauthorPoulogiannis, Georgiosen_US
dc.contributor.icrauthorJungwirth, Uteen_US


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