Oncotarget

Research Papers:

MERTK as a novel therapeutic target in head and neck cancer

Anne von Mässenhausen, Christine Sanders, Britta Thewes, Mario Deng, Angela Queisser, Wenzel Vogel, Glen Kristiansen, Stefan Duensing, Andreas Schröck, Friedrich Bootz, Peter Brossart, Jutta Kirfel, Lynn Heasley, Johannes Brägelmann and Sven Perner _

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Oncotarget. 2016; 7:32678-32694. https://doi.org/10.18632/oncotarget.8724

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Abstract

Anne von Mässenhausen1,2,3,*, Christine Sanders1,2,3,*, Britta Thewes1,2,3, Mario Deng4,5, Angela Queisser1,2,3, Wenzel Vogel4,5, Glen Kristiansen2,3, Stefan Duensing6, Andreas Schröck3,7, Friedrich Bootz3,7, Peter Brossart3,8, Jutta Kirfel2,3, Lynn Heasley9, Johannes Brägelmann1,3,8,*, Sven Perner4,5*

1Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany

2Institute of Pathology, University Hospital of Bonn, Bonn, Germany

3Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany

4Pathology of the University Hospital of Luebeck, Luebeck, Germany

5Leibniz Research Center Borstel, Borstel, Germany

6Department of Urology, University of Heidelberg, Heidelberg, Germany

7Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany

8Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany

9Department 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: [email protected]

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.


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