dc.contributor.author | Legrand, AJ | |
dc.contributor.author | Poletto, M | |
dc.contributor.author | Pankova, D | |
dc.contributor.author | Clementi, E | |
dc.contributor.author | Moore, J | |
dc.contributor.author | Castro-Giner, F | |
dc.contributor.author | Ryan, AJ | |
dc.contributor.author | O'Neill, E | |
dc.contributor.author | Markkanen, E | |
dc.contributor.author | Dianov, GL | |
dc.date.accessioned | 2018-03-27T09:22:05Z | |
dc.date.issued | 2018-03-02 | |
dc.identifier.citation | Oncotarget, 2018, 9 (17), pp. 13666 - 13681 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1607 | |
dc.identifier.eissn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.24446 | |
dc.description.abstract | Cancer-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.format | Electronic-eCollection | |
dc.format.extent | 13666 - 13681 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Impact Journals, LLC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-01-30 | |
rioxxterms.versionofrecord | 10.18632/oncotarget.24446 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncotarget | |
pubs.issue | 17 | |
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/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-status | Published | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Legrand, Arnaud | |