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http://hdl.handle.net/2445/185223
Title: | MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence |
Author: | Gabasa Ferràndez, Marta Radisky, Evette S Ikemori, Rafael Bertolini, Giulia Arshakyan, Marselina Hockla, Alexandra Duch, Paula Rondinone, Ornella Llorente, Alejandro Maqueda, Maria Dávalos, Albert Gavilán, Elena Perera Lluna, Alexandre Ramírez, Josep Gascón, Pere Reguart, Noemí Roz, Luca Radisky, Derek C Alcaraz Casademunt, Jordi |
Keywords: | Càncer de pulmó Tumors Fibroblasts Metal·loproteïnases Lung cancer Tumors Fibroblasts Metalloproteinases |
Issue Date: | 6-Mar-2021 |
Publisher: | Elsevier B.V. |
Abstract: | Large cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drives LCC cell growth and invasion. Here we identify MMP1 as overexpressed specifically in LCC cell lines, and we show that expression of MMP1 by LCC cells is necessary for induction of fibroblast senescence and consequent tumor promotion in both cell culture and mouse models. We also show that MMP1, in combination with TGF-β1, is sufficient to induce fibroblast senescence and consequent LCC promotion. Furthermore, we implicate PAR-1 and oxidative stress in MMP1/TGF-β1-induced TAF senescence. Our results establish an entirely new role for MMP1 in cancer, and support a novel therapeutic strategy in LCC based on targeting senescent TAFs. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.canlet.2021.01.028 |
It is part of: | Cancer Letters, 2021, vol. 507, p. 1-12 |
URI: | http://hdl.handle.net/2445/185223 |
Related resource: | https://doi.org/10.1016/j.canlet.2021.01.028 |
ISSN: | 0304-3835 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) Publicacions de projectes de recerca finançats per la UE |
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