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J Clin Invest. 2012 Apr;122(4):1529-40. doi: 10.1172/JCI61350. Epub 2012 Mar 1.

β₁Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy.

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  • 1OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.

Abstract

Integrin signaling critically contributes to the progression, growth, and therapy resistance of malignant tumors. Here, we show that targeting of β₁ 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 β₁ 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 β₁ integrins may provide therapeutic benefit to overcome tumor cell resistance to radiotherapy.

PMID:
22378044
[PubMed - indexed for MEDLINE]
PMCID:
PMC3314473
Free PMC Article
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