title: Implication of the Receptor Tyrosine Kinase AXL in Head and Neck Cancer Progression.
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.
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, 53127 Bonn, Germany. anne.vonmaessenhausen@gmail.com.|Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany. anne.vonmaessenhausen@gmail.com.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. anne.vonmaessenhausen@gmail.com.
authors.forename: Anne
authors.initials: A
authors.lastname: von Mässenhausen
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, 53127 Bonn, Germany. j.braegelmann@gmx.de.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. j.braegelmann@gmx.de.|Department of Hematology/Oncology/Rheumatology, University Hospital of Bonn, 53127 Bonn, Germany. j.braegelmann@gmx.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Institute of Pathology, University Hospital of Luebeck, 23538 Luebeck, Germany. hannah.stefanie.billig@gmail.com.|Leibniz Research Center Borstel, 23845 Borstel, Germany. hannah.stefanie.billig@gmail.com.
authors.forename: Hannah
authors.initials: H
authors.lastname: Billig
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, 53127 Bonn, Germany. britta.thewes@gmail.com.|Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany. britta.thewes@gmail.com.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. britta.thewes@gmail.com.
authors.forename: Britta
authors.initials: B
authors.lastname: Thewes
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, 53127 Bonn, Germany. queisserangela@googlemail.com.|Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany. queisserangela@googlemail.com.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. queisserangela@googlemail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Institute of Pathology, University Hospital of Luebeck, 23538 Luebeck, Germany. wenzelvogel@googlemail.com.|Leibniz Research Center Borstel, 23845 Borstel, Germany. wenzelvogel@googlemail.com.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany. Glen.Kristiansen@ukb.uni-bonn.de.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. Glen.Kristiansen@ukb.uni-bonn.de.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. Andreas.Schroeck@ukb.uni-bonn.de.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany. Andreas.Schroeck@ukb.uni-bonn.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. Friedrich.bootz@ukb.uni-bonn.de.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, 53127 Bonn, Germany. Friedrich.bootz@ukb.uni-bonn.de.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. peter.brossart@ukb.uni-bonn.de.|Department of Hematology/Oncology/Rheumatology, University Hospital of Bonn, 53127 Bonn, Germany. peter.brossart@ukb.uni-bonn.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany. jutta.kirfel@ukb.uni-bonn.de.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, 53127 Bonn, Germany. jutta.kirfel@ukb.uni-bonn.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.affiliation: Institute of Pathology, University Hospital of Luebeck, 23538 Luebeck, Germany. sven.perner@uksh.de.|Leibniz Research Center Borstel, 23845 Borstel, Germany. sven.perner@uksh.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001567:Benzocycloheptenes / Q000494:pharmacology* / Q000633:toxicity; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology* / Q000633:toxicity; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D000970:Antineoplastic Agents; D001567:Benzocycloheptenes; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D014230:Triazoles; C548378:bemcentinib; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL; BGB324; HNSCC; immunohistochemistry; receptor tyrosine kinase; targeted therapy