ArticleThe Journal of experimental medicine2016
Gankyrin has an antioxidative role through the feedback regulation of Nrf2 in hepatocellular carcinoma.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Gankyrin-Protein Interactions in GI Cancers: A Novel Target of New Therapeutics.Chronic diseases and translational medicine · 2025Review
- PIP5K1A Suppresses Ferroptosis and Induces Sorafenib Resistance by Stabilizing NRF2 in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KEAP1-NRF2 Interaction in Cancer: Competitive Interactors and Their Role in Carcinogenesis.Cancers · 2025Review
- The USP11/Nrf2 positive feedback loop promotes colorectal cancer progression by inhibiting mitochondrial apoptosis.Cell death & disease · 2024Article
- Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2.Experimental & molecular medicine · 2024Article
- Excessive SOX8 reprograms energy and iron metabolism to prime hepatocellular carcinoma for ferroptosis.Redox biology · 2024Article
- Nrf2, A Target for Precision Oncology in Cancer Prognosis and Treatment.Journal of cancer prevention · 2023Review
- Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1.Clinics (Sao Paulo, Brazil) · 2023Article
- Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma.Cancer science · 2022Article
- Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner.Cell death discovery · 2022Article
- Identification of ferroptosis-related genes for overall survival prediction in hepatocellular carcinoma.Scientific reports · 2022Article
- Nrf2/Keap1/ARE signaling: Towards specific regulation.Life sciences · 2022Review
- Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- Molecular Targets of Ferroptosis in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2021Review
- Beyond repression of Nrf2: An update on Keap1.Free radical biology & medicine · 2020Review
- SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling.Journal of cellular and molecular medicine · 2020Article
- The Clinicopathological and Prognostic Significance of Nrf2 and Keap1 Expression in Hepatocellular Carcinoma.Cancers · 2020Article
- Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis.International journal of molecular sciences · 2020Review
- Keap1 governs ageing-induced protein aggregation in endothelial cells.Redox biology · 2020Article
- Nestin regulates cellular redox homeostasis in lung cancer through the Keap1-Nrf2 feedback loop.Nature communications · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress status has a key role in hepatocellular carcinoma (HCC) development and progression. Normally, reactive oxygen species (ROS) levels are tightly controlled by an inducible antioxidant program that responds to cellular stressors. How HCC cells respond to excessive oxidative stress remains elusive. Here, we identified a feedback loop between gankyrin, an oncoprotein overexpressed in human HCC, and Nrf2 maintaining the homeostasis in HCC cells. Mechanistically, gankyrin was found to interact with the Kelch domain of Keap1 and effectively competed with Nrf2 for Keap1 binding. Increased expression of gankyrin in HCC cells blocked the binding between Nrf2 and Keap1, inhibiting the degradation of Nrf2 by proteasome. Interestingly, accumulation and translocation of Nrf2 increased the transcription of gankyrin through binding to the ARE elements in the promoter of gankyrin. The positive feedback regulation involving gankyrin and Nrf2 modulates a series of antioxidant enzymes, thereby lowering intracellular ROS and conferring a steadier intracellular environment, which prevents mitochondrial damage and cell death induced by excessive oxidative stress. Our results indicate that gankyrin is a regulator of cellular redox homeostasis and provide a link between oxidative stress and the development of HCC.
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