1b. Laryngoscope, 127:2460-2465, 2017.

Background Activating transcription factor-2 (ATF2) is associated with tumor progression, but is not well-studied in head and neck squamous cell carcinoma (HNSCC). Its effects in stress and its importance in other survival mechanisms were studied. Methods ATF2 expression and nuclear activation were confirmed in HNSCC. Following modulation of ATF2, in vitro effects on proliferation and chemosensitivity were studied. Effects on in vivo tumor growth and Interleukin 8 (IL-8) expression were determined. Tumor Necrosis Factor (TNF) alpha treatment was used to further evaluate cytokine production and chemosensitivity. Results Reductions of ATF2 resulted in significant nuclear p-ATF2 activation, cisplatin resistance and augmented IL-8 expression without affecting in vivo tumor growth. In this setting, TNF increases p-p38 phosphorylation and chemosensitivity while further enhancing IL-8 production. Conclusions Our data suggest regulatory roles for ATF2 in TNF-related mechanisms of HNSCC. Its perturbation and nuclear activation are associated with significant effects on survival and cytokine production.