ArticleThe Biochemical journal2020
NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Site-specific prevalence of the NFE2L2 mutation in esophageal squamous cell carcinoma.International journal of clinical oncology · 2025Article
- Luteolin protects against alcoholic liver injury by restoring NRF2 stability to suppress ACSS2 nuclear accumulation.NPJ science of food · 2025Article
- KLF13 promotes esophageal cancer progression and regulates triacylglyceride and free fatty acid metabolism through GPIHBP1.Cell death & disease · 2025Article
- Acetyl-CoA metabolism in cancer.Nature reviews. Cancer · 2023Review
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development.Discover oncology · 2022Review
- Alcohol-driven metabolic reprogramming promotes development of RORγt-deficient thymic lymphoma.Oncogene · 2022Article
- Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review.Journal of oncology · 2022Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Comment on article by Christina Puhr Hannah et al.: Clinical characteristics and comparison of the outcome in young versus older patients with upper gastrointestinal carcinoma.Journal of cancer research and clinical oncology · 2021Article
- Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.The Journal of pathology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Alcohol drinking is a leading risk factor for the development of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms of alcohol-associated ESCC remain poorly understood. One of the most commonly mutated genes in ESCC is nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2), which is a critical transcription factor regulating oxidative stress response and drug detoxification. When NRF2 is hyperactive in cancer cells, however, it leads to metabolic reprogramming, cell proliferation, chemoradioresistance, and poor prognosis. In this study, hyperactive NRF2 was found to up-regulate acetyl-CoA synthetase short-chain family members 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in ESCC cells and mouse esophagus. We also showed that knockdown of NRF2 or ACSS2 led to decreased ACSS2 expression, which in turn reduced the levels of acetyl-CoA and ATP with or without ethanol exposure. In addition, ethanol exposure enhanced lipid synthesis in ESCC cells. Moreover, we observed a change in the metabolic profile of ESCC cells exposed to ethanol as a result of their NRF2 or ACSS2 status. We further showed that ACSS2 contributed to the invasive capability of NRF2high ESCC cells exposed to ethanol. In conclusion, the NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on ESCC.
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Registered trials
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