Selective inhibition of EGFR downstream signaling reverses the irradiation-enhanced migration of HNSCC cells

Dominik Schuettler; Guido Piontek; Markus Wirth; Bernhard Haller; Rudolf Reiter; Gero Brockhoff; Anja Pickhard

Selective inhibition of EGFR downstream signaling reverses the irradiation-enhanced migration of HNSCC cells

Am J Cancer Res. 2015 Aug 15;5(9):2660-72. eCollection 2015.

Authors

Dominik Schuettler¹, Guido Piontek¹, Markus Wirth¹, Bernhard Haller², Rudolf Reiter³, Gero Brockhoff⁴, Anja Pickhard¹

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Technical University of Munich Ismaninger Str. 22, Muenchen 81675, Germany.
² Institute for Medical Statistics and Epidemiology, Technical University of Munich Ismaninger Straße 22, Muenchen 81675, Germany.
³ Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm Prittwitzstr. 43, Ulm 89075, Germany.
⁴ Department of Gynecology and Obstetrics, University of Regensburg Landshuter Str. 65, Regensburg 93053, Germany.

PMID: 26609474
PMCID: PMC4633896

Abstract

Irradiation, which is one of the standard therapies used to treat squamous cell carcinoma of the head and neck (HNSCC), has been linked to enhanced tumor migration in carcinomas. In this study, we demonstrated that irradiation induced the phosphorylation of AKT, p38 MAPK and ERK. The combined activation of these pathways caused inactivation of GSK3β kinase, resulting in enhanced tumor cell migration. Here, we describe that the exclusive and specific inhibition of just one of the aforementioned key signaling molecules is sufficient to restore GSK3β activity and to reduce radiation-induced migration in HNSCC. These data indicate that pharmacological inhibition of pathways targeting GSK3β could decrease radiation-induced cell migration in HNSCC and thus potentially reduce metastasis and locoregional recurrence in patients.

Keywords: GSK3β; Radiation; migration.