dc.contributor.author | Avgustinova, A | |
dc.contributor.author | Iravani, M | |
dc.contributor.author | Robertson, D | |
dc.contributor.author | Fearns, A | |
dc.contributor.author | Gao, Q | |
dc.contributor.author | Klingbeil, P | |
dc.contributor.author | Hanby, AM | |
dc.contributor.author | Speirs, V | |
dc.contributor.author | Sahai, E | |
dc.contributor.author | Calvo, F | |
dc.contributor.author | Isacke, CM | |
dc.date.accessioned | 2016-12-12T14:21:59Z | |
dc.date.issued | 2016-01-18 | |
dc.identifier.citation | Nature communications, 2016, 7 pp. 10305 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/336 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms10305 | |
dc.description.abstract | Stromal 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.format | Electronic | |
dc.format.extent | 10305 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | NIH 3T3 Cells | |
dc.subject | Fibroblasts | |
dc.subject | Animals | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Breast Neoplasms | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Female | |
dc.subject | Wnt Proteins | |
dc.title | Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-11-27 | |
rioxxterms.versionofrecord | 10.1038/ncomms10305 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-01-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Tumour Microenvironment | |
dc.contributor.icrauthor | Iravani, Marjan | |
dc.contributor.icrauthor | Gao, Qiong | |
dc.contributor.icrauthor | Isacke, Clare | |