NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma

Odera, Joab Otieno; Xiong, Zhaohui; Huang, Caizhi; Gu, Ning; Yang, Wenjun; Githanga, Jessie; Odera, Elizabeth; Paiboonrungruang, Chorlada; Chen, Xiaoxin

doi:10.1042/bcj20200452

Cited by 10 publications

(8 citation statements)

References 78 publications

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“…Ethanol has been shown to enhance the expression and nuclear localization of 5‐lipoxygenase and stimulate the biosynthesis of pro‐inflammatory leukotriene B4 in oral cancer cells [48]. Ethanol‐derived acetate may also feed into energy metabolism as a carbon source [49], or promote histone acetylation and thus regulate gene transcription [50]. Ethanol exposure increases the mutation rate through error‐prone polymerases [51].…”

Section: Discussionmentioning

confidence: 99%

Alcohol drinking inhibits NOTCH–PAX9 signaling in esophageal squamous epithelial cells

Shi

Ren

Chen

et al. 2021

The Journal of Pathology

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Alcohol drinking has been established as a major risk factor for esophageal diseases. Our previous study showed that ethanol exposure inhibited PAX9 expression in human esophageal squamous epithelial cells in vitro and in vivo. In this study, we aimed to investigate the molecular pathways through which alcohol drinking suppresses PAX9 in esophageal squamous epithelial cells. We first demonstrated the inhibition of NOTCH by ethanol exposure in vitro. NOTCH regulated PAX9 expression in KYSE510 and KYSE410 cells in vitro and in vivo. RBPJ and NOTCH intracellular domain (NIC) D1 ChIP‐PCR confirmed Pax9 as a direct downstream target of NOTCH signaling in mouse esophagus. NOTCH inhibition by alcohol drinking was further validated in mouse esophagus and human tissue samples. In conclusion, ethanol exposure inhibited NOTCH signaling and thus suppressed PAX9 expression in esophageal squamous epithelial cells in vitro and in vivo. Our data support a novel mechanism of alcohol‐induced esophageal injury through the inhibition of NOTCH–PAX9 signaling. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Alcohol drinking inhibits NOTCH–PAX9 signaling in esophageal squamous epithelial cells

Shi

Ren

Chen

et al. 2021

The Journal of Pathology

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“…In esophageal cancer cells and the mouse esophagus, knockout of either NRF2 or ACSS2 reduced ACSS2 expression, which subsequently decreased acetyl-CoA and ATP levels. Moreover, lipid synthesis in esophageal carcinoma cells was decreased, and the invasion ability of these cells was weakened [95].…”

Section: Gastrointestinal Cancermentioning

confidence: 99%

Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development

et al. 2022

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Acetyl-CoA synthetase 2 (ACSS2), an important member of the acetyl-CoA synthetase (ACSS) family, can catalyze the conversion of acetate to acetyl coenzyme A (acetyl-CoA). Currently, acetyl-CoA is considered an important intermediate metabolite in the metabolism of energy substrates. In addition, nutrients converge through acetyl-CoA into a common metabolic pathway, the tricarboxylic acid cycle and oxidative phosphorylation. Not only does ACSS2 play a crucial role in material energy metabolism, it is also involved in the regulation of various acetylation processes, such as regulation of histone and transcription factor acetylation. ACSS2-mediated regulation of acetylation is related to substance metabolism and tumorigenesis. In mammalian cells, ACSS2 utilizes intracellular acetate to synthesize acetyl-CoA, a step in the process of DNA and histone acetylation. In addition, studies in tumors have shown that cancer cells adapt to the growth conditions in the tumor microenvironment (TME) by activating or increasing the expression level of ACSS2 under metabolic stress. Therefore, this review mainly outlines the role of ACSS2 in substance metabolism and tumors and provides insights useful for investigating ACSS2 as a therapeutic target.

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“…Milada et al found that FA spectra changed in plasma phosphatidylcholine in esophageal squamous cell carcinoma patients, which might be correlated with abnormal fatty acid metabolism in cancer (e.g., altered de novo fatty acid synthesis, β -oxidation, desaturation, and extension). The above changes may be correlated with the prominent functioning of neoadjuvant chemotherapy [ 23 ].…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

“…The NRF2/ACSS2 axis will allow ESCC cells to exploit ethanol-derived acetate as their energy source. It can regulate downstream ethanol metabolism and metabolic reprogramming in ESCC, while inducing lipid synthesis and alcohol-related ESCC [ 23 ].…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

“…Alcohol is also a critical element in the development of esophageal squamous cell carcinoma. As indicated by the experiment of Odera et al, NRF2/ACSS2 axis mediated the metabolic effect of alcohol drinking on ESCC [ 23 ]. In brief, ACSS2 targets in patients with esophageal cancer may create superior survival benefits.…”

Section: Introduction To Esophageal Cancermentioning

confidence: 99%

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Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review

Cui

Cao

et al. 2022

Journal of Oncology

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Esophageal cancer is of high importance to occurrence, development, and treatment resistance. As evidenced by recent studies, pathways (e.g., Wnt/β-catenin, AMPK, and Hippo) are critical to the proliferation, differentiation, and self-renewal of esophageal cancer. In addition, the above pathways play a certain role in regulating esophageal cancer and act as potential therapeutic targets. Over the past few years, the function of lipid metabolism in controlling tumor cells and immune cells has aroused extensive attention. It has been reported that there are intricate interactions between lipid metabolism reprogramming between immune and esophageal cancer cells, whereas molecular mechanisms should be studied in depth. Immune cells have been commonly recognized as a vital player in the esophageal cancer microenvironment, having complex crosstalk with cancer cells. It is increasingly evidenced that the function of immune cells in the tumor microenvironment (TME) is significantly correlated with abnormal lipid metabolism. In this review, the latest findings in lipid metabolism reprogramming in TME are summarized, and the above findings are linked to esophageal cancer progression. Aberrant lipid metabolism and associated signaling pathways are likely to serve as a novel strategy to treat esophageal cancer through lipid metabolism reprogramming.

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NRF2/ACSS2 axis mediates the metabolic effect of alcohol drinking on esophageal squamous cell carcinoma

Cited by 10 publications

References 78 publications

Alcohol drinking inhibits NOTCH–PAX9 signaling in esophageal squamous epithelial cells

Alcohol drinking inhibits NOTCH–PAX9 signaling in esophageal squamous epithelial cells

Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development

Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review

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