We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.
- Authors
Arriola, E.; Cañadas, I.; Arumí-Uría, M.; Dómine, M.; Lopez-Vilariño, J. A.; Arpí, O.; Salido, M.; Menéndez, S.; Grande, E.; Hirsch, F. R.; Serrano, S.; Bellosillo, B.; Rojo, F.; Rovira, A.; Albanell, J.; Cañadas, I; Arumí-Uría, M; Dómine, M; Lopez-Vilariño, J A; Arpí, O
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
PHOSPHORYLATION; SMALL cell lung cancer; GROWTH factors; PROGNOSIS; HEALTH outcome assessment; CELL lines; GENETICS
- Publication
British Journal of Cancer, 2011, Vol 105, Issue 6, p814
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2011.298