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Genetics and Genomics

Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer

British Journal of Cancer volume 126, pages 1244–1252 (2022)Cite this article

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Abstract

Electrophilic and oxidative stress is caused when homeostatic mechanisms are disrupted. A major defense mechanism involves the activation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor encoded by the NFE2L2 gene, which can accelerate the detoxification of electrophilic carcinogens and prevent cancer and on the other hand in certain exposure contexts may exacerbate the carcinogenic process. NRF2-target genes activated under these conditions can be used as biomarkers of stress signalling, while activation of NRF2 can also reveal the epigenetic mechanisms that modulate NFE2L2 expression. Epigenetic mechanisms that regulate NFE2L2 and the gene for its adaptor protein KEAP1 include DNA methylation, histone modifications and microRNA. Understanding the activation of the NRF2-KEAP1 signalling pathway in human lung cancer, its epigenetic regulation and its role in oncogenesis is the subject of this review.

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Fig. 1: Regulation of NRF2 Expression Under Different Conditions.
Fig. 2: Regulation of KEAP1 and NRF2.
Fig. 3: Percentage of KEAP1, NFE2L2 and CUL3 somatic mutations across the different lung cancer subtypes.

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Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

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Acknowledgements

This work was supported by P30-ES013508 and R01-ES029294 (awarded to TMP) from the National Institute of Environmental Health Sciences (NIEHS) at the NIH. The article represents the views of the authors and not the official views of NIH.

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  1. Department of Systems Pharmacology & Translational Therapeutics, Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nuria Camiña & Trevor M. Penning

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Camiña, N., Penning, T.M. Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer. Br J Cancer 126, 1244–1252 (2022). https://doi.org/10.1038/s41416-021-01642-0

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