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dc.contributor.authorPRIMAC, Ien_US
dc.contributor.authorMAQUOI, Een_US
dc.contributor.authorBLACHER, Sen_US
dc.contributor.authorHELJASVAARA, Ren_US
dc.contributor.authorVan Deun, Janen_US
dc.contributor.authorSmeland, Hilde Ytre-Haugeen_US
dc.contributor.authorCANALE, Aen_US
dc.contributor.authorLOUIS, Ten_US
dc.contributor.authorStuhr, Linda Elin Birkhaugen_US
dc.contributor.authorSOUNNI, NEen_US
dc.contributor.authorCATALDO, Den_US
dc.contributor.authorPIHLAJANEMI, Ten_US
dc.contributor.authorPEQUEUX, Cen_US
dc.contributor.authorDE WEAVER, Oen_US
dc.contributor.authorGullberg, Donalden_US
dc.contributor.authorNoel, Agnesen_US
dc.date.accessioned2020-04-30T09:44:10Z
dc.date.available2020-04-30T09:44:10Z
dc.date.issued2019
dc.PublishedPRIMAC, MAQUOI, BLACHER, HELJASVAARA, Van Deun J, Smeland HB, CANALE, LOUIS, Stuhr LEB, SOUNNI, CATALDO, PIHLAJANEMI, PEQUEUX, DE WEAVER, Gullberg D, Noel A. Stromal integrin α11 regulates PDGFR-β signaling and promotes breast cancer progression.. Journal of Clinical Investigation. 2019;129(11):4609-4628eng
dc.identifier.issn1558-8238
dc.identifier.issn0021-9738
dc.identifier.urihttps://hdl.handle.net/1956/22056
dc.description.abstractCancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors, such as breast cancer (BC). Herein, we identify an integrin α11/PDGFRβ–positive CAF subset displaying tumor-promoting features in BC. In the preclinical MMTV-PyMT mouse model, integrin α11 deficiency led to a drastic reduction of tumor progression and metastasis. A clear association between integrin α11 and PDGFRβ was found at both transcriptional and histological levels in BC specimens. High stromal integrin α11/PDGFRβ expression was associated with high grades and poorer clinical outcome in human BC patients. Functional assays using 5 CAF subpopulations (1 murine, 4 human) revealed that integrin α11 promotes CAF invasion and CAF-induced tumor cell invasion upon PDGF-BB stimulation. Mechanistically, the proinvasive activity of integrin α11 relies on its ability to interact with PDGFRβ in a ligand-dependent manner and to promote its downstream JNK activation, leading to the production of tenascin C, a proinvasive matricellular protein. Pharmacological inhibition of PDGFRβ and JNK impaired tumor cell invasion induced by integrin α11+ CAFs. Collectively, our study uncovers an integrin α11+ subset of protumoral CAFs that exploits the PDGFRβ/JNK signaling axis to promote tumor invasiveness in BC.en_US
dc.language.isoengeng
dc.publisherAmerican Society for Clinical Investigationeng
dc.titleStromal integrin α11 regulates PDGFR-β signaling and promotes breast cancer progressionen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2019-11-25T09:15:04Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019, American Society for Clinical Investigation
dc.identifier.cristin1751691
dc.source.journalJournal of Clinical Investigation


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