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dc.contributor.authorTang, H
dc.contributor.authorLeung, L
dc.contributor.authorSaturno, G
dc.contributor.authorViros, A
dc.contributor.authorSmith, D
dc.contributor.authorDi Leva, G
dc.contributor.authorMorrison, E
dc.contributor.authorNiculescu-Duvaz, D
dc.contributor.authorLopes, F
dc.contributor.authorJohnson, L
dc.contributor.authorDhomen, N
dc.contributor.authorSpringer, C
dc.contributor.authorMarais, R
dc.date.accessioned2017-05-02T10:06:03Z
dc.date.issued2017-04-18
dc.identifier.citationNature communications, 2017, 8 pp. 14909 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/625
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms14909
dc.description.abstractLysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623.
dc.formatElectronic
dc.format.extent14909 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectCell Membrane
dc.subjectAnimals
dc.subjectDogs
dc.subjectHumans
dc.subjectMice
dc.subjectRats
dc.subjectNeoplasms
dc.subjectNeoplasm Metastasis
dc.subjectDisease Progression
dc.subjectAminopropionitrile
dc.subjectEpidermal Growth Factor
dc.subjectProtein-Lysine 6-Oxidase
dc.subjectEnzyme Inhibitors
dc.subjectBiosensing Techniques
dc.subjectSignal Transduction
dc.subjectCell Proliferation
dc.subjectEnzyme Activation
dc.subjectModels, Biological
dc.subjectTransforming Growth Factor beta1
dc.subjectMatrilin Proteins
dc.subjectErbB Receptors
dc.subjectHigh-Temperature Requirement A Serine Peptidase 1
dc.titleLysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.
dc.typeJournal Article
dcterms.dateAccepted2017-02-09
rioxxterms.versionofrecord10.1038/ncomms14909
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-04-18
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNot 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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamGene & Oncogene Targetingen_US
dc.contributor.icrauthorSpringer, Carolineen
dc.contributor.icrauthorNiculescu-Duvaz, Danen


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