TY  - JOUR
A1  - Pickhard, Anja
A1  - Siegl, Michael
A1  - Baumann, Alexander
A1  - Huhn, Maximilian
A1  - Wirth, Markus
A1  - Reiter, Rudolf
A1  - Rudelius, Martina
A1  - Piontek, Guido
A1  - Brockhoff, Gero
T1  - The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism
JF  - Oncotarget
N2  - Objectives: The aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines.
Materials and methods: First, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples.
The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting.
Results: Immunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27).
Conclusion: This study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.
KW  - aurora kinase A polymorphism
KW  - aurorakinase B
KW  - cetuximab
KW  - HNSCC
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120757
VL  - 5
IS  - 14
ER  - 
TY  - JOUR
A1  - Schiefler, Carlotta
A1  - Piontek, Guido
A1  - Doescher, Johannes
A1  - Schuettler, Dominik
A1  - Mißlbeck, Martin
A1  - Rudelius, Martina
A1  - Haug, Anna
A1  - Reiter, Rudolf
A1  - Brockhoff, Gero
A1  - Pickhard, Anja
T1  - Inhibition of SphK1 reduces radiation-induced migration and enhances sensitivity to cetuximab treatment by affecting the EGFR/SphK1 crosstalk
JF  - Oncotarget
N2  - SphK1 is known to play a role in tumor progression, resistance to radiochemotherapy, and migration patterns. As the overall survival rates of squamous cell carcinoma of the head and neck (HNSCC) remain poor due to limitations in surgery and irradiation and chemotherapy resistance, SphK1 is an important enzyme to investigate. The purpose of this study was to elucidate the impact of SphK1 on irradiation efficacy of HNSCC in-vitro with emphasis on EGFR signaling. By immunhistochemical staining we found a positive correlation between EGFR and SphK1 expression in patient specimens. In colony formation assays irradiation sensitive cell lines showed a poor response to cetuximab, an EGFR inhibitor, and SKI-II, a SphK1 inhibitor, and vice versa. In irradiation sensitive cells an enhanced reduction of cell migration and survival was found upon simultaneous targeting of EGFR and SphK1. In the present study, we elucidated a linkage between the two signaling pathways with regard to the efficacy of cetuximab treatment and the impact on the migration behavior of tumor cells. We investigated the biological impact of inhibiting these pathways and examined the biochemical implications after different treatments. An understanding of the processes involved could help to improve the treatment of patients with HNSCC.
KW  - radiation-induced migration
KW  - radiation
KW  - HNSCC
KW  - EGFR
KW  - SphK1
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120929
SN  - 1949-2553
VL  - 5
IS  - 20
ER  -