MERTK as a novel therapeutic target in head and neck cancer

// Anne von Massenhausen 1, 2, 3, * , Christine Sanders 1, 2, 3, * , Britta Thewes 1, 2, 3 , Mario Deng 4, 5 , Angela Queisser 1, 2, 3 , Wenzel Vogel 4, 5 , Glen Kristiansen 2, 3 , Stefan Duensing 6 , Andreas Schrock 3, 7 , Friedrich Bootz 3, 7 , Peter Brossart 3, 8 , Jutta Kirfel 2, 3 , Lynn Heasley 9 , Johannes Bragelmann 1, 3, 8, * , Sven Perner 4, 5 * 1 Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany 2 Institute of Pathology, University Hospital of Bonn, Bonn, Germany 3 Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany 4 Pathology of the University Hospital of Luebeck, Luebeck, Germany 5 Leibniz Research Center Borstel, Borstel, Germany 6 Department of Urology, University of Heidelberg, Heidelberg, Germany 7 Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany 8 Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany 9 Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA * These authors have contributed equally to this work Correspondence to: Sven Perner, email: Sven.Perner@uksh.de Keywords: head and neck cancer, MERTK, targeted therapy Abbreviations: HNSCC, head and neck squamous cell carcinoma; MERTK, MER proto-oncogene tyrosine kinase; FAK, focal adhesion kinase; TCGA, The Cancer Genome Atlas Received: January 07, 2016 Accepted: March 28, 2016 Published: April 13, 2016 ABSTRACT Although head and neck cancer (HNSCC) is the sixth most common tumor entity worldwide therapy options remain limited leading to 5-year survival rates of only 50 %. MERTK is a promising therapeutic target in several tumor entities, however, its role in HNSCC has not been described yet. The aim of our study was to investigate the biological significance of MERTK and to evaluate its potential as a novel therapeutic target in this dismal tumor entity. In two large HNSCC cohorts (n=537 and n=520) we found that MERTK is overexpressed in one third of patients. In-vitro, MERTK overexpression led to increased proliferation, migration and invasion whereas MERTK inhibition with the small molecule inhibitor UNC1062 or MERTK knockdown reduced cell motility via the small GTPase RhoA. Taken together, we are the first to show that MERTK is frequently overexpressed in HNSCC and plays an important role in tumor cell motility. It might therefore be a potential target for selected patients suffering from this dismal tumor entity.