Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2) transcription factor is recognized for its pro-survival and cell protective role upon exposure to oxidative, chemical, or metabolic stresses. Nrf2 controls a number of cellular processes such as proliferation, differentiation, apoptosis, autophagy, lipid synthesis, and metabolism and glucose metabolism and is a target of activation in chronic diseases like diabetes, neurodegenerative, and inflammatory diseases. The dark side of Nrf2 is revealed when its regulation is imbalanced (e.g., via oncogene activation or mutations) and under such conditions constitutively active Nrf2 promotes cancerogenesis, metastasis, and radio- and chemoresistance. When there is no stress, Nrf2 is instantly degraded via Keap1-Cullin 3 (Cul3) pathway but despite this, cells exhibit a basal activation of Nrf2 target genes. It is yet not clear how Nrf2 maintains the expression of its targets under homeostatic conditions. Here, we found a stable 105 kDa Nrf2 form that is resistant to Keap1-Cul3-mediated degradation and translocates to the nucleus of lung cancer cells. RNA-Seq analysis indicate that it might originate from the exon 2 or exon 3-truncated transcripts. This stable 105 kDa Nrf2 form might help explain the constitutive activity of Nrf2 under normal cellular conditions.

• Klíčová slova
• Nrf2 antibodies, Nrf2 detection, Nrf2 migration in SDS-PAGE,
• Publikační typ
• časopisecké články MeSH

Significance: Nuclear factor erythroid 2 (NFE2)-related factor 2 (NFE2L2, or NRF2) is a transcription factor predominantly affecting the expression of antioxidant genes. NRF2 plays a significant role in the control of redox balance, which is crucial in cancer cells. NRF2 activation regulates numerous cancer hallmarks, including metabolism, cancer stem cell characteristics, tumor aggressiveness, invasion, and metastasis formation. We review the molecular characteristics of the NRF2 pathway and discuss its interactions with the cancer hallmarks previously listed. Recent Advances: The noncanonical activation of NRF2 was recently discovered, and members of this pathway are involved in carcinogenesis. Further, cancer-related changes (e.g., metabolic flexibility) that support cancer progression were found to be redox- and NRF2 dependent. Critical Issues: NRF2 undergoes Janus-faced behavior in cancers. The pro- or antineoplastic effects of NRF2 are context dependent and essentially based on the specific molecular characteristics of the cancer in question. Therefore, systematic investigation of NRF2 signaling is necessary to clarify its role in cancer etiology. The biggest challenge in the NRF2 field is to determine which cancers can be targeted for better clinical outcomes. Further, large-scale genomic and transcriptomic studies are missing to correlate the clinical outcome with the activity of the NRF2 system. Future Directions: To exploit NRF2 in a clinical setting in the future, the druggable members of the NRF2 pathway should be identified. In addition, it will be important to study how the modulation of the NRF2 system interferes with cytostatic drugs and their combinations.

• Klíčová slova
• NRF2, breast cancer, cancer, cancer metabolism, reactive species,
• MeSH
• antioxidancia metabolismus   MeSH
• energetický metabolismus * MeSH
• epigeneze genetická MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• hormony metabolismus   MeSH
• lidé MeSH
• metabolické sítě a dráhy * MeSH
• mikro RNA genetika   MeSH
• mutace MeSH
• nádorové biomarkery MeSH
• nádorové kmenové buňky metabolismus   MeSH
• nádory etiologie   metabolismus   patologie   MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• signální dráha UPR MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• faktor 2 související s NF-E2 MeSH
• hormony MeSH
• mikro RNA MeSH
• nádorové biomarkery MeSH
• NFE2L2 protein, human MeSH Prohlížeč

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.

• Klíčová slova
• NF-E2-related factor 2, hepatocellular carcinoma, oxidative stress, redox homeostasis, transcription factor,
• MeSH
• aktivace transkripce * MeSH
• analýza přežití MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• genové regulační sítě MeSH
• hepatocelulární karcinom diagnóza   genetika   mortalita   patologie   MeSH
• karcinogeneze genetika   metabolismus   patologie   MeSH
• KEAP-1 genetika   metabolismus   MeSH
• lidé MeSH
• mutace MeSH
• nádorové buněčné linie MeSH
• nádory jater diagnóza   genetika   mortalita   patologie   MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• KEAP-1 MeSH
• KEAP1 protein, human MeSH Prohlížeč
• NFE2L2 protein, human MeSH Prohlížeč