MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.
dc.contributor.author | Arriola, E. | |
dc.contributor.author | Cañadas, I. | |
dc.contributor.author | Arumí-Uría, M. | |
dc.contributor.author | Dómine, M. | |
dc.contributor.author | Grande-Pulido, E. | |
dc.contributor.author | Albanell, J. | |
dc.date.accessioned | 2024-01-24T11:06:24Z | |
dc.date.available | 2024-01-24T11:06:24Z | |
dc.date.issued | 2011 | |
dc.description.abstract | Background: Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target. Methods: To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed. Results: In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a multivariate analysis. Conclusions: MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease. | spa |
dc.description.extent | 935 KB | spa |
dc.identifier.doi | 10.1038/bjc.2011.298 | spa |
dc.identifier.issn | 1532-1827 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3812 | |
dc.language.iso | eng | spa |
dc.publisher | British Journal of Cancer | spa |
dc.relation.publisherversion | https://www.nature.com/articles/bjc2011298 | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.accessRights | metadata only access | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | SMUR | spa |
dspace.entity.type | Publication |