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  -