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dc.contributor.authorAvgustinova, A
dc.contributor.authorIravani, M
dc.contributor.authorRobertson, D
dc.contributor.authorFearns, A
dc.contributor.authorGao, Q
dc.contributor.authorKlingbeil, P
dc.contributor.authorHanby, AM
dc.contributor.authorSpeirs, V
dc.contributor.authorSahai, E
dc.contributor.authorCalvo, F
dc.contributor.authorIsacke, CM
dc.date.accessioned2016-12-12T14:21:59Z
dc.date.issued2016-01-18
dc.identifier.citationNature communications, 2016, 7 pp. 10305 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/336
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms10305
dc.description.abstractStromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis. Mechanistically, Wnt7a-mediated fibroblast activation is not dependent on classical Wnt signalling. Instead, we demonstrate that Wnt7a potentiates TGFβ receptor signalling both in 3D in vitro and in vivo models, thus highlighting the interaction between two of the key signalling pathways in development and disease. Importantly, in clinical breast cancer cohorts, tumour cell Wnt7a expression correlates with a desmoplastic, poor-prognosis stroma and poor patient outcome.
dc.formatElectronic
dc.format.extent10305 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectNIH 3T3 Cells
dc.subjectFibroblasts
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectFemale
dc.subjectWnt Proteins
dc.titleTumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness.
dc.typeJournal Article
dcterms.dateAccepted2015-11-27
rioxxterms.versionofrecord10.1038/ncomms10305
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-01-18
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/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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Microenvironment
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Microenvironment
pubs.publication-statusPublished
pubs.volume7
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biologyen_US
icr.researchteamTumour Microenvironmenten_US
dc.contributor.icrauthorCalvo, Fernandoen
dc.contributor.icrauthorAvgustinova, Alexandraen
dc.contributor.icrauthorIsacke, Clareen
dc.contributor.icrauthorGao, Qiongen
dc.contributor.icrauthorIravani, Marjanen


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