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Int. J. Mol. Sci. 2017, 18(1), 7; doi:10.3390/ijms18010007

Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression

1
Section of Prostate Cancer Research, University Hospital of Bonn, 53127 Bonn, Germany
2
Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany
3
Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany
4
Department of Hematology/Oncology/Rheumatology, University Hospital of Bonn, 53127 Bonn, Germany
5
Institute of Pathology, University Hospital of Luebeck, 23538 Luebeck, Germany
6
Leibniz Research Center Borstel, 23845 Borstel, Germany
7
Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Hsueh-Wei Chang
Received: 7 November 2016 / Revised: 7 December 2016 / Accepted: 14 December 2016 / Published: 22 December 2016
(This article belongs to the Special Issue Tumor Targeting Therapy and Selective Killing)
View Full-Text   |   Download PDF [1282 KB, uploaded 22 December 2016]   |  

Abstract

Head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge and identification of novel therapeutic targets is necessary. The receptor tyrosine kinase AXL has been implicated in several tumor entities and a selective AXL small molecule inhibitor (BGB324) is currently being tested in clinical trials for patients suffering from non-small cell lung cancer or acute myeloid leukemia. Our study investigates AXL expression during HNSCC progression and its use as a potential therapeutic target in HNSCC. AXL protein expression was determined in a HNSCC cohort (n = 364) using immunohistochemical staining. For functional validation, AXL was either overexpressed or inhibited with BGB324 in HNSCC cell lines to assess proliferation, migration and invasion. We found AXL protein expression increasing during tumor progression with highest expression levels in recurrent tumors. In HNSCC cell lines in vitro, AXL overexpression increased migration as well as invasion. Both properties could be reduced through treatment with BGB324. In contrast, proliferation was neither affected by AXL overexpression nor by inhibition with BGB324. Our patient-derived data and in vitro results show that, in HNSCC, AXL is important for the progression to more advanced tumor stages. Moreover, they suggest that AXL could be a target for precision medicine approaches in this dismal tumor entity. View Full-Text
Keywords: HNSCC; AXL; receptor tyrosine kinase; targeted therapy; BGB324; immunohistochemistry HNSCC; AXL; receptor tyrosine kinase; targeted therapy; BGB324; immunohistochemistry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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von Mässenhausen, A.; Brägelmann, J.; Billig, H.; Thewes, B.; Queisser, A.; Vogel, W.; Kristiansen, G.; Schröck, A.; Bootz, F.; Brossart, P.; Kirfel, J.; Perner, S. Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression. Int. J. Mol. Sci. 2017, 18, 7.

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