Receptor tyrosine kinase MET as potential target of multi-kinase inhibitor and radiosensitizer sorafenib in HNSCC
- Link:
- Autor/in:
- Erscheinungsjahr:
- 2019
- Medientyp:
- Text
- Beschreibung:
-
BACKGROUND: The multi-kinase inhibitor sorafenib displays antitumoral effects in head and neck squamous cell carcinoma (HNSCC); however, the targeted kinases are unknown. Here we aimed to identify those kinases to determine the mechanism of sorafenib-mediated effects and establish candidate biomarkers for patient stratification.
METHODS: The effects of sorafenib and MET inhibitors crizotinib and SU11274 were analyzed using a slide-based antibody array, Western blotting, proliferation, and survival assays. X-rays were used for irradiations.
RESULTS: Sorafenib inhibited auto-phosphorylation of epidermal growth factor receptor and MET, which has not been described previously. MET expression in HNSCC cells was not always associated with activity/phosphorylation. Furthermore, sorafenib-dependent cell kill and radiosensitization was not associated with MET level. Although MET inhibitors blocked proliferation, they caused only mild cytotoxicity and no radiosensitization.
CONCLUSION: We identified MET as a new potential target of sorafenib. However, MET inhibition is not the cause for sorafenib-mediated cytotoxicity or radiosensitization.
- Lizenz:
-
- info:eu-repo/semantics/restrictedAccess
- Quellsystem:
- Forschungsinformationssystem des UKE
Interne Metadaten
- Quelldatensatz
- oai:pure.atira.dk:publications/0504ce74-56ee-4104-89f5-40a8923a7b56