Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression
| Autor: | Wenzel Vogel, Angela Queisser, Andreas Schröck, Britta Thewes, Anne von Mässenhausen, Sven Perner, Glen Kristiansen, Peter Brossart, Johannes Brägelmann, Jutta Kirfel, Friedrich Bootz, Hannah Billig |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology HNSCC AXL receptor tyrosine kinase targeted therapy BGB324 immunohistochemistry Receptor tyrosine kinase lcsh:Chemistry 0302 clinical medicine Cell Movement lcsh:QH301-705.5 Spectroscopy biology Myeloid leukemia General Medicine Computer Science Applications Benzocycloheptenes Head and Neck Neoplasms 030220 oncology & carcinogenesis Immunohistochemistry medicine.medical_specialty Antineoplastic Agents Catalysis Article Inorganic Chemistry 03 medical and health sciences Cell Line Tumor Proto-Oncogene Proteins medicine Humans Physical and Theoretical Chemistry Molecular Biology Protein Kinase Inhibitors Cell Proliferation Organic Chemistry Head and neck cancer Carcinoma Receptor Protein-Tyrosine Kinases Triazoles medicine.disease Head and neck squamous-cell carcinoma Axl Receptor Tyrosine Kinase In vitro stomatognathic diseases 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Tumor progression Cell culture Cancer research biology.protein |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 18; Issue 1; Pages: 7 International Journal of Molecular Sciences, Vol 18, Iss 1, p 7 (2016) |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|