The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer

By E. Kansanen, Suvi M. Kuosmanen, Hanna M. Leinonen, A. Levonen. Redox Biology, 2013

1,258 citations recorded by the source corpus.

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells. We also briefly summarize the consequences of constitutive Nrf2 activation in cancer cells and how this can be exploited in cancer gene therapy.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3b7333c8d335f825a503829efdc3528ef3abb637

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Citations in the corpus

Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism (2016, background): “The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this co”
The Roles of NRF2 in Modulating Cellular Iron Homeostasis (2017, background): “Many reviews have focused on NRF2-mediated cytoprotection as well as KEAP1 and non-KEAP1-mediated NRF2 activation (34, 38, 56, 58, 86, 171).”
Glutathione: new roles in redox signaling for an old antioxidant (2014, background): “…(Pineda-Molina et al., 2001), heat shock factor 1 (HSF1; Jacquier-Sarlin and Polla, 1996; Anckar and Sistonen, 2011), and NE2FL2 (Itoh et al., 2004; Kansanen et al., 2013) together with the upstream mediators (dead receptors; Sullivan et al., 2000) of phosphorylative cascade, MAPKs (Filomeni et…”
Glutathione metabolism in cancer progression and treatment resistance (2018, background): “Several mechanisms appear to be responsible for increased NRF2 activity in cancers: somatic mutations in KEAP1, CUL3, or NRF2; epigenetic silencing of KEAP; transcriptional NRF2 up-regulation through oncogene-dependent signaling and modification of KEAP1 by metabolic alterations (Kansanen et al., 20”
The Development of the Concept of Ferroptosis (2018, neutral): “of antioxidant enzymes [213], and glutathione and thioredoxin antioxidant systems are commonly activated in cancers [214,215].”
The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state (2015, background): “tion of Nrf2 by oncogenes such as K-ras, B-raf or c-myc [87].”
One-Carbon Metabolism in Health and Disease. (2017, background): “In lung cancer, ATF4 is commonly activated by NRF2 due to mutations in the NRF2 suppressor KEAP1 (DeNicola et al., 2015; Kansanen et al., 2013).”