Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that resides at sites of integrin clustering, contributing to focal-adhesion scaffolding and growth-factor-dependent signals transmission. Despite the increasing importance of FAK in human cancer, there is however a lack of knowledge about its role in Non Small Cell Lung Cancer (NSCLC). To this purpose, the main aims of this project were: 1) to investigate FAK expression and its clinical significance in NSCLC 2) to understand the molecular mechanisms by which FAK exploits its role. The study population consisted of 60 NSCLCs obtained from patients who underwent surgical resection. Immunoistochemistry was used to analyze FAK expression and localisation in formalin-fixed and paraffin-embedded NSCLC biopsies. FAK mRNAs were determined by real-time RT-PCR in frozen tissue specimens and protein expression was also evaluated by western blotting in 16 homogenates. Altogether, the three differenttechniques showed that FAK is up-regulated in NSCLC and correlates with higher stages of disease. This increase resulted a specific event, p53-independent. Moreover, FAK up-regulation correlated with JNK and pJNK increase and with the induction of MMP-2 and MMP-9 in NSCLC. These evidences suggest that FAK may have a role not only in the development and maintenance but also in the progression of NSCLC. It may therefore represent a novel target for inhibitory therapies in lung cancer.
|Titolo:||High expression of focal adhesion kinase is associated with non small cell lung cancer progression|
|Supervisori e coordinatori interni:||VILLA, MARIA LUISA|
|Data di pubblicazione:||2006|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
Settore MED/04 - Patologia Generale
|Citazione:||High expression of focal adhesion kinase is associated with non small cell lung cancer progression ; Silvano Bosari, Maria Luisa Villa. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE E TECNOLOGIE BIOMEDICHE, 2006. ((19. ciclo, Anno Accademico 2005/2006.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|