β 1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Integrin signaling critically contributes to the progression, growth, and therapy resistance of malignant tumors. Here, we show that targeting of β 1 integrins with inhibitory antibodies enhances the sensitivity to ionizing radiation and delays the growth of human head and neck squamous cell carcinoma cell lines in 3D cell culture and in xenografted mice. Mechanistically, dephosphorylation of focal adhesion kinase (FAK) upon inhibition of β 1 integrin resulted in dissociation of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling and induced cell rounding, leading to radiosensitization. Thus, these findings suggest that robust and selective pharmacological targeting of β 1 integrins may provide therapeutic benefit to overcome tumor cell resistance to radiotherapy.

Details

OriginalspracheEnglisch
Seiten (von - bis)1529-1540
Seitenumfang12
FachzeitschriftJournal of Clinical Investigation
Jahrgang122
Ausgabenummer4
PublikationsstatusVeröffentlicht - 2 Apr. 2012
Peer-Review-StatusJa

Externe IDs

PubMed 22378044
ORCID /0000-0001-5684-629X/work/166326478
ORCID /0000-0003-1776-9556/work/171065830

Schlagworte

Ziele für nachhaltige Entwicklung

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