title: uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.
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.
authors.affiliation: Grupo d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Infections and Cancer Unit, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO) and Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pavón
authors.affiliation: Grupo d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Arroyo-Solera
authors.affiliation: Grupo d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Maria Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.affiliation: Grupo d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.affiliation: Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.|Department of Otorrinolaryngology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.affiliation: Grupo d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator
keywords: SERPINE1; head and neck cancer; prognosis; uPA; uPAR