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dc.contributor.authorKnott, SRV
dc.contributor.authorWagenblast, E
dc.contributor.authorKhan, S
dc.contributor.authorKim, SY
dc.contributor.authorSoto, M
dc.contributor.authorWagner, M
dc.contributor.authorTurgeon, M-O
dc.contributor.authorFish, L
dc.contributor.authorErard, N
dc.contributor.authorGable, AL
dc.contributor.authorMaceli, AR
dc.contributor.authorDickopf, S
dc.contributor.authorPapachristou, EK
dc.contributor.authorD'Santos, CS
dc.contributor.authorCarey, LA
dc.contributor.authorWilkinson, JE
dc.contributor.authorHarrell, JC
dc.contributor.authorPerou, CM
dc.contributor.authorGoodarzi, H
dc.contributor.authorPoulogiannis, G
dc.contributor.authorHannon, GJ
dc.date.accessioned2018-02-19T12:36:24Z
dc.date.issued2018-02-07
dc.identifier.citationNature, 2018, 554 (7692), pp. 378 - 381
dc.identifier.issn0028-0836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1289
dc.identifier.eissn1476-4687en_US
dc.identifier.doi10.1038/nature25465en_US
dc.description.abstractUsing a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.
dc.formatPrint-Electronic
dc.format.extent378 - 381
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectLung Neoplasms
dc.subjectProstatic Neoplasms
dc.subjectNeoplasm Invasiveness
dc.subjectNeoplasm Metastasis
dc.subjectDisease Models, Animal
dc.subjectDisease Progression
dc.subjectAsparaginase
dc.subjectAspartate-Ammonia Ligase
dc.subjectAsparagine
dc.subjectPrognosis
dc.subjectReproducibility of Results
dc.subjectRNA Interference
dc.subjectBiological Availability
dc.subjectFemale
dc.subjectMale
dc.subjectEpithelial-Mesenchymal Transition
dc.titleAsparagine bioavailability governs metastasis in a model of breast cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-12-15
rioxxterms.versionofrecord10.1038/nature25465
rioxxterms.licenseref.startdate2018-02-07en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature
pubs.issue7692
pubs.notes6 months
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume554en_US
pubs.embargo.terms6 months
icr.researchteamSignalling & Cancer Metabolismen_US
dc.contributor.icrauthorTurgeon, Marc-Olivieren
dc.contributor.icrauthorPoulogiannis, Georgiosen


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