RT Journal Article
T1 MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence.
A1 Gabasa, Marta
A1 Radisky, Evette S
A1 Ikemori, Rafael
A1 Bertolini, Giulia
A1 Arshakyan, Marselina
A1 Hockla, Alexandra
A1 Duch, Paula
A1 Rondinone, Ornella
A1 Llorente, Alejandro
A1 Maqueda, Maria
A1 Davalos, Albert
A1 Gavilán, Elena
A1 Perera, Alexandre
A1 Ramírez, Josep
A1 Gascón, Pere
A1 Reguart, Noemí
A1 Roz, Luca
A1 Radisky, Derek C
A1 Alcaraz, Jordi
K1 Cancer-associated fibroblasts
K1 MMP1
K1 TGF-β
K1 lung cancer
K1 senescence
AB 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.
YR 2021
FD 2021-03-06
LK http://hdl.handle.net/10668/17329
UL http://hdl.handle.net/10668/17329
LA en
DS RISalud
RD Apr 19, 2025