ArticleOncogene2020
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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Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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21 citing papers in PubMed, 26 citations in OpenAlex.
- Homoisoflavanone Delays Colorectal Cancer Progression via DNA Damage-Induced Mitochondrial Apoptosis and Parthanatos-Like Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Recent advances in novel targeting mechanisms for colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation.Journal of the Egyptian National Cancer Institute · 2025Article
- GPR35-mediated metabolic reprogramming promotes tumorigenesis in digestive cancers.Frontiers in immunology · 2025Review
- New developments in AMPK and mTORC1 cross-talk.Essays in biochemistry · 2024Review
- In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies.Scientific reports · 2024Article
- Pioglitazone as a Possible Treatment forBiomolecules · 2024Review
- Mitochondria-Targeted Nanoadjuvants Induced Multi-Functional Immune-Microenvironment Remodeling to Sensitize Tumor Radio-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Copper in the colorectal cancer microenvironment: pioneering a new era of cuproptosis-based therapy.Frontiers in oncology · 2024Review
- Elevated basal AMP-activated protein kinase activity sensitizes colorectal cancer cells to growth inhibition by metformin.Open biology · 2023Article
- Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma.Frontiers in genetics · 2023Article
- CPT1A promotes anoikis resistance in esophageal squamous cell carcinoma via redox homeostasis.Redox biology · 2022Article
- Lymphatic metastasis-associated circRNA‒miRNA‒mRNA network for exploring the pathogenesis and therapeutic target of triple negative breast cancer based on whole-transcriptome sequencing analysis: an experimental verification study.Journal of translational medicine · 2022Article
- Luteolin Synergistically Enhances Antitumor Activity of Oxaliplatin in Colorectal Carcinoma via AMPK Inhibition.Antioxidants (Basel, Switzerland) · 2022Article
- Low Expression of AGPAT5 Is Associated With Clinical Stage and Poor Prognosis in Colorectal Cancer and Contributes to Tumour Progression.Clinical Medicine Insights. Oncology · 2022Article
- Compound C, a Broad Kinase Inhibitor Alters Metabolic Fingerprinting of Extra Cellular Matrix Detached Cancer Cells.Frontiers in oncology · 2021Article
- A Novel Biological Activity of the STAT3 Inhibitor Stattic in Inhibiting Glutathione Reductase and Suppressing the Tumorigenicity of Human Cervical Cancer Cells via a ROS-Dependent Pathway.OncoTargets and therapy · 2021Article
- Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications.World journal of gastroenterology · 2020Review
- How does mTOR sense glucose starvation? AMPK is the usual suspect.Cell death discovery · 2020Review
- Review
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Authors and funding
28 authors at 2 institutions in 2 countries.
Ying-Nan Wang *Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Yun-Xin Lu *Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Jie Liu *Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
Ying Jin *Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Hui-Chang BiSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
Qi ZhaoSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0002-8683-6145
Ze-Xian LiuSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0001-9698-0610
Ying-Qin LiDepartment of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
Jia-Jia HuSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Hui ShengSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Yi-Ming JiangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
Chao ZhangDepartment of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Feng TianDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yang ChenSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Zhi-Zhong PanDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Gong ChenDepartment of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Zhao-Lei ZengSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0003-4420-5625
Kai-Yan LiuSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Marcia OgasawaraDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA.
Jin-Ping YunDepartment of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Huai-Qiang JuSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0003-1713-5465
Jian-Xiong FengSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Dan XieSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0003-2242-3138
Song GaoSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.ORCID http://orcid.org/0000-0001-7427-6681
Wei-Hua JiaSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.
Scott KopetzDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. skopetz@mdanderson.org.
Rui-Hua XuSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. xurh@sysucc.org.cn.ORCID http://orcid.org/0000-0001-9771-8534
Feng WangSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China. wangfeng@sysucc.org.cn.
Sun Yat-sen University · CNThe University of Texas MD Anderson Cancer Center · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MNCI NIH HHS P30 CA016672
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 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-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.
Indexed as
AgedAMP-Activated Protein KinasesAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinogenesisCell Line, TumorCell SurvivalColorectal NeoplasmsDrug SynergismFemaleGene Knockdown TechniquesGlutathione ReductaseHumansKaplan-Meier EstimateMaleMiceAMP-Activated Protein KinasesGlutathione ReductaseOxaliplatinPRKAA1 protein, humanReactive Oxygen SpeciesRNA, Small InterferingThreonine
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