dc.contributor.author | PRIMAC, I | en_US |
dc.contributor.author | MAQUOI, E | en_US |
dc.contributor.author | BLACHER, S | en_US |
dc.contributor.author | HELJASVAARA, R | en_US |
dc.contributor.author | Van Deun, Jan | en_US |
dc.contributor.author | Smeland, Hilde Ytre-Hauge | en_US |
dc.contributor.author | CANALE, A | en_US |
dc.contributor.author | LOUIS, T | en_US |
dc.contributor.author | Stuhr, Linda Elin Birkhaug | en_US |
dc.contributor.author | SOUNNI, NE | en_US |
dc.contributor.author | CATALDO, D | en_US |
dc.contributor.author | PIHLAJANEMI, T | en_US |
dc.contributor.author | PEQUEUX, C | en_US |
dc.contributor.author | DE WEAVER, O | en_US |
dc.contributor.author | Gullberg, Donald | en_US |
dc.contributor.author | Noel, Agnes | en_US |
dc.date.accessioned | 2020-04-30T09:44:10Z | |
dc.date.available | 2020-04-30T09:44:10Z | |
dc.date.issued | 2019 | |
dc.Published | PRIMAC, 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):4609-4628 | eng |
dc.identifier.issn | 1558-8238 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://hdl.handle.net/1956/22056 | |
dc.description.abstract | Cancer-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.iso | eng | eng |
dc.publisher | American Society for Clinical Investigation | eng |
dc.title | Stromal integrin α11 regulates PDGFR-β signaling and promotes breast cancer progression | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2019-11-25T09:15:04Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2019, American Society for Clinical Investigation | |
dc.identifier.cristin | 1751691 | |
dc.source.journal | Journal of Clinical Investigation | |