Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets
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Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets. / Bußmann, Lara; Hoffer, Konstantin; von Bargen, Clara Marie; Droste, Conrad; Lange, Tobias; Kemmling, Julia; Schröder-Schwarz, Jennifer; Vu, Anh Thu; Akingunsade, Lara; Nollau, Peter; Rangarajan, Savithri; de Wijn, Rik; Oetting, Agnes; Müller, Christian; Böckelmann, Lukas Clemens; Zech, Henrike Barbara; Berger, Joanna Caroline; Möckelmann, Nikolaus; Busch, Chia-Jung; Böttcher, Arne; Gatzemeier, Fruzsina; Klinghammer, Konrad; Simnica, Donjete; Binder, Mascha; Struve, Nina; Rieckmann, Thorsten; Schumacher, Udo; Clauditz, Till Sebastian; Betz, Christian Stephan; Petersen, Cordula; Rothkamm, Kai; Münscher, Adrian; Kriegs, Malte.
in: INT J CANCER, Jahrgang 149, Nr. 5, 01.09.2021, S. 1166 - 1180.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets
AU - Bußmann, Lara
AU - Hoffer, Konstantin
AU - von Bargen, Clara Marie
AU - Droste, Conrad
AU - Lange, Tobias
AU - Kemmling, Julia
AU - Schröder-Schwarz, Jennifer
AU - Vu, Anh Thu
AU - Akingunsade, Lara
AU - Nollau, Peter
AU - Rangarajan, Savithri
AU - de Wijn, Rik
AU - Oetting, Agnes
AU - Müller, Christian
AU - Böckelmann, Lukas Clemens
AU - Zech, Henrike Barbara
AU - Berger, Joanna Caroline
AU - Möckelmann, Nikolaus
AU - Busch, Chia-Jung
AU - Böttcher, Arne
AU - Gatzemeier, Fruzsina
AU - Klinghammer, Konrad
AU - Simnica, Donjete
AU - Binder, Mascha
AU - Struve, Nina
AU - Rieckmann, Thorsten
AU - Schumacher, Udo
AU - Clauditz, Till Sebastian
AU - Betz, Christian Stephan
AU - Petersen, Cordula
AU - Rothkamm, Kai
AU - Münscher, Adrian
AU - Kriegs, Malte
N1 - Julia Kemmling: Anatomie und Exp. Morphologie; Lara Akingunsade: Strahlentherapie
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.
AB - Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.
KW - Aberrant kinase activity
KW - Functional kinome profiling
KW - Head and neck cancer
KW - Src-family kinases
KW - personalized targeted therapy
UR - https://onlinelibrary.wiley.com/doi/10.1002/ijc.33961
U2 - 10.1002/ijc.33606
DO - 10.1002/ijc.33606
M3 - SCORING: Journal article
C2 - 33890294
VL - 149
SP - 1166
EP - 1180
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 5
ER -