title: Activation of Keap1/Nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells.
abstract: 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.
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Longfei
authors: L
authors: Huo
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Chia-Wei
authors: CW
authors: Li
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Tzu-Hsuan
authors: TH
authors: Huang
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Yung Carmen
authors: YC
authors: Lam
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Weiya
authors: W
authors: Xia
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Chun
authors: C
authors: Tu
authors: Graduate Institute for Cancer Biology and Center for Molecular Medicine, China Medical University Taichung 404, Taiwan.
authors: Wei-Chao
authors: WC
authors: Chang
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030 ; Graduate Institute for Cancer Biology and Center for Molecular Medicine, China Medical University Taichung 404, Taiwan ; Department of Biotechnology, Asia University Taichung, Taiwan.
authors: Jennifer L
authors: JL
authors: Hsu
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Dung-Fang
authors: DF
authors: Lee
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Lei
authors: L
authors: Nie
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Hirohito
authors: H
authors: Yamaguchi
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Yan
authors: Y
authors: Wang
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Jingyu
authors: J
authors: Lang
authors: Graduate Institute for Cancer Biology and Center for Molecular Medicine, China Medical University Taichung 404, Taiwan.
authors: Long-Yuan
authors: LY
authors: Li
authors: Genomics Research Center, Academia Sinica Nankang, Taipei 105, Taiwan.
authors: Chung-Hsuan
authors: CH
authors: Chen
authors: Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030.
authors: Lopa
authors: L
authors: Mishra
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Houston, TX 77030 ; Graduate Institute for Cancer Biology and Center for Molecular Medicine, China Medical University Taichung 404, Taiwan ; Department of Biotechnology, Asia University Taichung, Taiwan.
authors: Mien-Chie
authors: MC
authors: Hung
keywords: EGFR; Keap1; Nrf2; cancer; ubiquitination
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