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

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

SUBMITTER: Eke I

PROVIDER: S-EPMC3314473 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Eke Iris I Deuse Yvonne Y Hehlgans Stephanie S Gurtner Kristin K Krause Mechthild M Baumann Michael M Shevchenko Anna A Sandfort Veit V Cordes Nils N

The Journal of clinical investigation 20120301 4

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 pr ...[more]

PMID: 22378044

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