Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors.
Concetta Di MauroAda PesapaneLuigi FormisanoRoberta RosaValentina D'AmatoPaola CiciolaAlberto ServettoRoberta MarcianoRoberta Clara OrsiniFrancesca MonteleoneNicola ZambranoGabriella FontaniniAdele ServadioGiuseppe PignataroLucia GrumettoAntonio LavecchiaDario BruzzeseAntonino IaccarinoGiancarlo TronconeBianca Maria VenezianiNunzia MontuoriSabino De PlacidoRoberto BiancoPublished in: Scientific reports (2017)
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation. Therefore, we investigated the role of uPAR expression in RAS mutated NSCLC and CRC cells. In this study we provided evidence, for the first time, that RAS mutational condition is functionally correlated to uPAR overexpression in NSCLC and CRC cancer cell lines and patient-derived tissue samples. Moreover, oncogenic features related to uPAR overexpression in RAS mutated NSCLC and CRC, such as adhesion, migration and metastatic process may be targeted, in vitro and in vivo, by new anti-uPAR small molecules, specific inhibitors of uPAR-vitronectin interaction. Therefore, anti-uPAR drugs could represent an effective pharmacological strategy for NSCLC and CRC patients carrying RAS mutations.
Keyphrases
- poor prognosis
- small cell lung cancer
- wild type
- long non coding rna
- tyrosine kinase
- advanced non small cell lung cancer
- epidermal growth factor receptor
- binding protein
- brain metastases
- cell migration
- end stage renal disease
- cell proliferation
- squamous cell carcinoma
- cell surface
- endothelial cells
- induced apoptosis
- oxidative stress
- mass spectrometry
- drug delivery
- high resolution
- drug induced
- pluripotent stem cells