title: Caveolin-1-negative head and neck squamous cell carcinoma primary tumors display increased epithelial to mesenchymal transition and prometastatic properties.
abstract: Distant metastases arise in 20-30% of patients with squamous cell carcinoma of the head and neck (HNSCC) in the 2 years following treatment. Therapeutic options are limited and the outcome of the patients is poor. The identification of predictive biomarkers of patient at risk for distant metastasis and therapies are urgently needed. We previously identified a clinical subgroup, called "R1" characterized by high propensity for rapid distant metastasis. Here, we showed that "R1" patients do not or at very low level express caveolin-1 (Cav1). Low or no expression of Cav1 is of bad prognosis. Disappearance of Cav1 enables cells to undergo epithelial-mesenchymal transition (EMT). EMT is associated with enhanced migration and invasion. Our study uncovered a new target, α5β1 integrin. Targeting α5β1 integrins might not only prevent metastasis of HNSCC but also delay the development of the primary tumor by reducing tumor cell viability. Cav1 detection might be taken into consideration in the future in the clinic not only to identify patients at high risk of metastasis but also to select patient who might benefit from an anti-integrin therapy.
authors.affiliation: Laboratoire de Biologie Tumorale, EA 3430 Université de Strasbourg, CRLC Paul Strauss, Strasbourg, France.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Jung
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ray
authors.affiliation: Laboratoire de Biologie Tumorale, EA 3430 Université de Strasbourg, CRLC Paul Strauss, Strasbourg, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Ramolu
authors.affiliation: Laboratoire de Biologie Tumorale, EA 3430 Université de Strasbourg, CRLC Paul Strauss, Strasbourg, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Macabre
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Simon
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Noulet
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Anne-Florence
authors.initials: AF
authors.lastname: Blandin
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Renner
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Choulier
authors.affiliation: Institute for Advanced Study and Center of Integrated Protein Studies, Technische Universität München, Department Chemie, Garching, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.affiliation: Laboratoire de Biologie Tumorale, EA 3430 Université de Strasbourg, CRLC Paul Strauss, Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Abecassis
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Dontenwill
authors.affiliation: Université de Strasbourg, LBP, CNRS UMR 7213, Illkirch, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martin
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D034622:RNA Interference; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1; D039081:Integrin alpha5beta1
keywords: caveolin-1; head and neck cancer; integrins; metastasis