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AMPK?1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

ABSTRACT: Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPK?1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPK?1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPK?1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPK?1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPK?1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

SUBMITTER: Wang YN

PROVIDER: S-EPMC6962094 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

Wang Ying-Nan YN Lu Yun-Xin YX Liu Jie J Jin Ying Y Bi Hui-Chang HC Zhao Qi Q Liu Ze-Xian ZX Li Ying-Qin YQ Hu Jia-Jia JJ Sheng Hui H Jiang Yi-Ming YM Zhang Chao C Tian Feng F Chen Yang Y Pan Zhi-Zhong ZZ Chen Gong G Zeng Zhao-Lei ZL Liu Kai-Yan KY Ogasawara Marcia M Yun Jin-Ping JP Ju Huai-Qiang HQ Feng Jian-Xiong JX Xie Dan D Gao Song S Jia Wei-Hua WH Kopetz Scott S Xu Rui-Hua RH Wang Feng F

Oncogene 20190917 3

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxid ...[more]

PMID: 31530934

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Dataset Information

AMPK?1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

Publications

AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

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