title: Selective inhibition of EGFR downstream signaling reverses the irradiation-enhanced migration of HNSCC cells.
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.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich Ismaninger Str. 22, Muenchen 81675, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schuettler
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich Ismaninger Str. 22, Muenchen 81675, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Piontek
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich Ismaninger Str. 22, Muenchen 81675, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wirth
authors.affiliation: Institute for Medical Statistics and Epidemiology, Technical University of Munich Ismaninger Straße 22, Muenchen 81675, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm Prittwitzstr. 43, Ulm 89075, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Reiter
authors.affiliation: Department of Gynecology and Obstetrics, University of Regensburg Landshuter Str. 65, Regensburg 93053, Germany.
authors.forename: Gero
authors.initials: G
authors.lastname: Brockhoff
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich Ismaninger Str. 22, Muenchen 81675, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Pickhard
keywords: GSK3β; Radiation; migration