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dc.contributor.authorMessaritou, G
dc.contributor.authorEast, L
dc.contributor.authorRoghi, C
dc.contributor.authorIsacke, CM
dc.contributor.authorYarwood, H
dc.date.accessioned2018-07-31T14:16:00Z
dc.date.issued2009-11
dc.identifier.citationJournal of cell science, 2009, 122 (Pt 22), pp. 4042 - 4048
dc.identifier.issn0021-9533
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2234
dc.identifier.eissn1477-9137
dc.identifier.doi10.1242/jcs.044305
dc.description.abstractThe molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent on secreted and membrane-bound collagenases, the other on receptor-mediated collagen internalisation and intracellular processing. Despite the established importance of both pathways, the functional interaction between them is largely unknown. We demonstrate here, that the collagen internalisation receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. We show close correlation between Endo180 expression, collagen accumulation and regulation of MT1-MMP cell-surface localisation and activity. We directly demonstrate, using collagen inhibition studies and non-collagen-binding mutants of Endo180, that the molecular mechanism underlying this regulation is the ability of Endo180 to bind and/or internalise collagens, rather than by acting as an interaction partner for pro-uPA and its receptor uPAR. These studies strongly support a functional interaction between two distinct collagen degradation pathways, define a novel mechanism regulating MT1-MMP activity and might have important implications for organised collagen clearance in the pericellular environment.
dc.formatPrint-Electronic
dc.format.extent4042 - 4048
dc.languageeng
dc.language.isoeng
dc.subjectCell Line
dc.subjectHumans
dc.subjectCollagen
dc.subjectReceptors, Mitogen
dc.subjectRNA, Small Interfering
dc.subjectSignal Transduction
dc.subjectEndocytosis
dc.subjectDown-Regulation
dc.subjectProtein Binding
dc.subjectMutation
dc.subjectMatrix Metalloproteinase 2
dc.subjectMatrix Metalloproteinase 14
dc.subjectUrokinase-Type Plasminogen Activator
dc.subjectReceptors, Urokinase Plasminogen Activator
dc.titleMembrane type-1 matrix metalloproteinase activity is regulated by the endocytic collagen receptor Endo180.
dc.typeJournal Article
rioxxterms.versionofrecord10.1242/jcs.044305
rioxxterms.licenseref.startdate2009-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of cell science
pubs.issuePt 22
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
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.publication-statusPublished
pubs.volume122
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biologyen_US
dc.contributor.icrauthorYarwood, Helenen
dc.contributor.icrauthorIsacke, Clareen


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