Receptor tyrosine kinase MET as potential target of multi-kinase inhibitor and radiosensitizer sorafenib in HNSCC
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Receptor tyrosine kinase MET as potential target of multi-kinase inhibitor and radiosensitizer sorafenib in HNSCC. / 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.
in: HEAD NECK-J SCI SPEC, Jahrgang 41, Nr. 1, 01.2019, S. 208-215.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Receptor tyrosine kinase MET as potential target of multi-kinase inhibitor and radiosensitizer sorafenib in HNSCC
AU - Beizaei, Kaweh
AU - Gleißner, Lisa
AU - Hoffer, Konstantin
AU - Bußmann, Lara
AU - Vu, Anh Thu
AU - Steinmeister, Leonhard
AU - Laban, Simon
AU - Möckelmann, Nikolaus
AU - Münscher, Adrian
AU - Petersen, Cordula
AU - Rothkamm, Kai
AU - Kriegs, Malte
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1002/hed.25440
DO - 10.1002/hed.25440
M3 - SCORING: Journal article
C2 - 30552828
VL - 41
SP - 208
EP - 215
JO - HEAD NECK-J SCI SPEC
JF - HEAD NECK-J SCI SPEC
SN - 1043-3074
IS - 1
ER -