Activation of Keap1/Nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells

American Journal of Translational Research

Jingyu Lang¹  Lopa Mishra¹  Yung Carmen Lam¹  Tzu-Hsuan Huang¹  Long-Yuan Li¹  Lei Nie¹  Hirohito Yamaguchi¹  Chung-Hsuan Chen¹  Wei-Chao Chang¹  Chia-Wei Li¹  Weiya Xia¹  Dung-Fang Lee¹  Jennifer L Hsu¹  Longfei Huo¹  Mien-Chie Hung¹  Yan Wang¹  Chun Tu¹ 

关键词: EGFR;    Keap1;    Nrf2;    cancer;    ubiquitination;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Nuclear translocation of EGFR has been shown to be important for tumor cell growth, survival, and therapeutic resistance. Previously, we detected the association of EGFR with Keap1 in the nucleus. Keap1 is a Kelch-like ECH-associated protein, which plays an important role in cellular response to chemical and oxidative stress by regulating Nrf2 protein stability and nuclear translocation. In this study, we investigate the role of EGFR in regulating Keap1/Nrf2 cascade in the nucleus and provide evidence to show that nuclear EGFR interacts with and phosphorylates nuclear Keap1 to reduce its nuclear protein level. The reduction of nuclear Keap1 consequently stabilizes nuclear Nrf2 and increases its transcriptional activity in cancer cells, which contributes to tumor cell resistance to chemotherapy.

【 授权许可】

Unknown