uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

// Miguel Angel Pavón 1,2,3 , Irene Arroyo-Solera 1,3 , Maria Virtudes Céspedes 1,3 , Isolda Casanova 1,3 , Xavier León 3,4 and Ramón Mangues 1,3 1 Grupo d’Oncogènesi i Antitumorals, lnstitut d’Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain 2 Infections and Cancer Unit, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO) and Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain 3 Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain 4 Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Correspondence to: Ramón Mangues, email: // Xavier León, email: // Keywords : head and neck cancer, uPA, uPAR, SERPINE1, prognosis Received : May 05, 2016 Accepted : June 13, 2016 Published : June 30, 2016 Abstract There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes. We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs.