Molecular Mechanisms Underlying Hepatocellular Carcinoma Induction by Aberrant NRF2 Activation-Mediated Transcription Networks: Interaction of NRF2-KEAP1 Controls the Fate of Hepatocarcinogenesis

• Published in: International journal of molecular sciences 2020-07, Vol.21 (15), p.5378
• Main Authors: Haque, Effi, Karim, M Rezaul, Salam Teeli, Aamir, Śmiech, Magdalena, Leszczynski, Paweł, Winiarczyk, Dawid, Parvanov, Emil D, Atanasov, Atanas G, Taniguchi, Hiroaki
• Format: Article
• Language: English
• Subjects: Adapter proteins; Antioxidants; Apoptosis; Binding sites; Cadmium telluride; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell Line, Tumor; Detoxification; Gene expression; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Hepatocellular carcinoma; Homeostasis; Humans; Infections; Kelch-Like ECH-Associated Protein 1 - genetics; Kelch-Like ECH-Associated Protein 1 - metabolism; Kinases; Leucine zipper proteins; Liver; Liver cancer; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Malignancy; Molecular modelling; Mutation; NF-E2-related factor 2; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Oxidation-Reduction; Oxidative Stress; Prognosis; Quantum dots; redox homeostasis; Review; Signal Transduction; Survival Analysis; Transcription activation; transcription factor; Transcription factors; Transcriptional Activation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155378

NF-E2-related factor 2 (NRF2) is a basic leucine zipper transcription factor, a master regulator of redox homeostasis regulating a variety of genes for antioxidant and detoxification enzymes. NRF2 was, therefore, initially thought to protect the liver from oxidative stress. Recent studies, however, have revealed that mutations in NRF2 cause aberrant accumulation of NRF2 in the nucleus and exert the upregulation of NRF2 target genes. Moreover, among all molecular changes in hepatocellular carcinoma (HCC), NRF2 activation has been revealed as a more prominent pathway contributing to the progression of precancerous lesions to malignancy. Nevertheless, how its activation leads to poor prognosis in HCC patients remains unclear. In this review, we provide an overview of how aberrant activation of NRF2 triggers HCC development. We also summarize the emerging roles of other NRF family members in liver cancer development.