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

• Published in: British journal of cancer Vol. 126; no. 9; pp. 1244 - 1252
• Main Authors: Camiña, Nuria, Penning, Trevor M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2022; Nature Publishing Group
• Subjects: 631/67/1612; 692/4028/67; Adaptor proteins; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinogens; Detoxification; DNA Methylation; Drug Resistance; Epidemiology; Epigenesis, Genetic; Epigenetics; Histones; Humans; Kelch-Like ECH-Associated Protein 1 - genetics; Kelch-Like ECH-Associated Protein 1 - metabolism; Lung cancer; Lung Neoplasms - genetics; miRNA; Molecular Medicine; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Oncology; Oxidative stress; Oxidative Stress - genetics; Review; Review Article; Signal transduction; Tumorigenesis
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-021-01642-0

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.