title: MERTK as a novel therapeutic target in head and neck cancer.
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.
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: von Mässenhausen
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Sanders
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Thewes
authors.affiliation: Pathology of The University Hospital of Luebeck, Luebeck, Germany.|Leibniz Research Center Borstel, Borstel, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Pathology of The University Hospital of Luebeck, Luebeck, Germany.|Leibniz Research Center Borstel, Borstel, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Urology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.affiliation: Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Heasley
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Pathology of The University Hospital of Luebeck, Luebeck, Germany.|Leibniz Research Center Borstel, Borstel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012307:Risk Factors; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult; D000076202:c-Mer Tyrosine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C586274:UNC1062; C066737:RHOA protein, human; C097072:MERTK protein, human; D000076202:c-Mer Tyrosine Kinase; D020742:rhoA GTP-Binding Protein
keywords: MERTK; head and neck cancer; targeted therapy