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dc.contributor.authorLegrand, AJ
dc.contributor.authorPoletto, M
dc.contributor.authorPankova, D
dc.contributor.authorClementi, E
dc.contributor.authorMoore, J
dc.contributor.authorCastro-Giner, F
dc.contributor.authorRyan, AJ
dc.contributor.authorO'Neill, E
dc.contributor.authorMarkkanen, E
dc.contributor.authorDianov, GL
dc.date.accessioned2018-03-27T09:22:05Z
dc.date.issued2018-03
dc.identifier.citationOncotarget, 2018, 9 (17), pp. 13666 - 13681
dc.identifier.issn1949-2553
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1607
dc.identifier.eissn1949-2553
dc.identifier.doi10.18632/oncotarget.24446
dc.description.abstractCancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as they promote tumour growth and metastatic potential. However, CAF targeting is complicated by the lack of knowledge-based strategies aiming to selectively eliminate these cells. There is a growing body of evidence suggesting that a pro-inflammatory microenvironment (e.g. ROS and cytokines) promotes CAF formation during tumorigenesis, although the exact mechanisms involved remain unclear. In this study, we reveal that a prolonged pro-inflammatory stimulation causes a de facto deficiency in base excision repair, generating unrepaired DNA strand breaks and thereby triggering an ATF4-dependent reprogramming of normal fibroblasts into CAF-like cells. Based on the phenotype of in vitro -generated CAFs, we demonstrate that midostaurin, a clinically relevant compound, selectively eliminates CAF-like cells deficient in base excision repair and prevents their stimulatory role in cancer cell growth and migration.
dc.formatElectronic-eCollection
dc.format.extent13666 - 13681
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePersistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts.
dc.typeJournal Article
dcterms.dateAccepted2018-01-30
rioxxterms.versionofrecord10.18632/oncotarget.24446
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncotarget
pubs.issue17
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/Cell Death and Immunity
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/Cell Death and Immunity
pubs.publication-statusPublished
pubs.volume9
pubs.embargo.termsNot known
icr.researchteamCell Death and Immunityen_US
dc.contributor.icrauthorLegrand, Arnauden


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0