MERTK as a novel therapeutic target in head and neck cancer

Oncotarget. 2016 May 31;7(22):32678-94. doi: 10.18632/oncotarget.8724.

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.

Keywords: MERTK; head and neck cancer; targeted therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • 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 / drug therapy
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Morpholines / pharmacology
  • Mutation
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / pharmacology
  • RNA Interference
  • Risk Factors
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • Sulfonamides / pharmacology
  • Time Factors
  • Transfection
  • Up-Regulation
  • Young Adult
  • c-Mer Tyrosine Kinase / antagonists & inhibitors
  • c-Mer Tyrosine Kinase / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Morpholines
  • Protein Kinase Inhibitors
  • Sulfonamides
  • UNC1062
  • RHOA protein, human
  • MERTK protein, human
  • c-Mer Tyrosine Kinase
  • rhoA GTP-Binding Protein