unc1062 and Carcinoma--Squamous-Cell

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; c-Mer Tyrosine Kinase; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Child; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Mutation; Neoplasm Invasiveness; Proportional Hazards Models; Protein Kinase Inhibitors; rhoA GTP-Binding Protein; Risk Factors; RNA Interference; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Sulfonamides; Time Factors; Transfection; Up-Regulation; Young Adult