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dc.contributor.authorFerrari, N
dc.contributor.authorRanftl, R
dc.contributor.authorChicherova, I
dc.contributor.authorSlaven, ND
dc.contributor.authorMoeendarbary, E
dc.contributor.authorFarrugia, AJ
dc.contributor.authorLam, M
dc.contributor.authorSemiannikova, M
dc.contributor.authorWestergaard, MCW
dc.contributor.authorTchou, J
dc.contributor.authorMagnani, L
dc.contributor.authorCalvo, F
dc.date.accessioned2018-12-17T11:26:20Z
dc.date.issued2019-01-10
dc.identifier.citationNature communications, 2019, 10 (1), pp. 130 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2973
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-018-07987-0
dc.description.abstractAggressive behaviours of solid tumours are highly influenced by the tumour microenvironment. Multiple signalling pathways can affect the normal function of stromal fibroblasts in tumours, but how these events are coordinated to generate tumour-promoting cancer-associated fibroblasts (CAFs) is not well understood. Here we show that stromal expression of Dickkopf-3 (DKK3) is associated with aggressive breast, colorectal and ovarian cancers. We demonstrate that DKK3 is a HSF1 effector that modulates the pro-tumorigenic behaviour of CAFs in vitro and in vivo. DKK3 orchestrates a concomitant activation of β-catenin and YAP/TAZ. Whereas β-catenin is dispensable for CAF-mediated ECM remodelling, cancer cell growth and invasion, DKK3-driven YAP/TAZ activation is required to induce tumour-promoting phenotypes. Mechanistically, DKK3 in CAFs acts via canonical Wnt signalling by interfering with the negative regulator Kremen and increasing cell-surface levels of LRP6. This work reveals an unpredicted link between HSF1, Wnt signalling and YAP/TAZ relevant for the generation of tumour-promoting CAFs.
dc.formatElectronic
dc.format.extent130 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCells, Cultured
dc.subjectCell Line
dc.subjectAnimals
dc.subjectMice, Transgenic
dc.subjectHumans
dc.subjectMice, Nude
dc.subjectNeoplasms
dc.subjectIntercellular Signaling Peptides and Proteins
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectTrans-Activators
dc.subjectMembrane Proteins
dc.subjectPhosphoproteins
dc.subjectTranscription Factors
dc.subjectChemokines
dc.subjectGene Expression Profiling
dc.subjectbeta Catenin
dc.subjectLow Density Lipoprotein Receptor-Related Protein-6
dc.subjectWnt Signaling Pathway
dc.subjectCancer-Associated Fibroblasts
dc.subjectHeat Shock Transcription Factors
dc.titleDickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts.
dc.typeJournal Article
dcterms.dateAccepted2018-12-10
rioxxterms.versionofrecord10.1038/s41467-018-07987-0
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Microenvironment
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Microenvironment
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics
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.volume10
pubs.embargo.termsNot known
icr.researchteamTumour Microenvironmenten_US
icr.researchteamTranslational Oncogenomicsen_US
dc.contributor.icrauthorCalvo, Fernandoen
dc.contributor.icrauthorLam, Maxineen
dc.contributor.icrauthorSemiannikova, Mariaen


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