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Receptor tyrosine kinase MET as potential target of multi‐kinase inhibitor and radiosensitizer sorafenib in HNSCC
Author(s) -
Beizaei Kaweh,
Gleißner Lisa,
Hoffer Konstantin,
Bußmann Lara,
Vu Anh Thu,
Steinmeister Leonhard,
Laban Simon,
Möckelmann Nikolaus,
Münscher Adrian,
Petersen Cordula,
Rothkamm Kai,
Kriegs Malte
Publication year - 2019
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.25440
Subject(s) - sorafenib , cancer research , radiosensitizer , kinase , head and neck squamous cell carcinoma , tyrosine kinase inhibitor , tyrosine kinase , receptor tyrosine kinase , medicine , mapk/erk pathway , chemistry , pharmacology , oncology , hepatocellular carcinoma , receptor , radiation therapy , head and neck cancer , cancer , biochemistry
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.