Abstract 5404: Metabolic stress played a role in dasatinib-induced EGFR degradation and apoptosis in head and neck cancer.

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is a worldwide disease with aggressive course and dismal outcome. Dasatinib, a Bcr-abl and Src in hibitor, has been approved clinically for CML and shown activities against solid tumors in vitro. In our recent work, degradation of epidermal growth factor receptor (EGFR) plays a role in dasatinib-induced apoptosis in HNSCC cells. We further revealed the role of metabolic stress in dasatinib-induced EGFR degradation and apoptosis. Dasatinib decreased cellular ATP, and activated AMPK activation and induced endoplasmic reticulum stress (ER stress) as well. Inhibition or knockdown of AMPK reversed dasatinib-induced EGFR degradation, and pharmacological activation of AMPK led to ER stress and EGFR degradation. Addition of ER stress inhibitor to dasatinib reversed EGFR degradation and apoptosis, and pharmacologic activation of ER stress resulted in EGFR degradation. In conclusion, metabolic stress may play a role in dasatinib-induced EGFR degradation and apoptosis in HNSCC cells. Citation Format: Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Kuen-Feng Chen, Ann-Lii Cheng, Ching-Chow Chen. Metabolic stress played a role in dasatinib-induced EGFR degradation and apoptosis in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5404. doi:10.1158/1538-7445.AM2013-5404