Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.

ABSTRACT: Redox regulators are emerging as critical mediators of lung tumorigenesis. NRF2 and its negative regulator KEAP1 are commonly mutated in human lung cancers, leading to NRF2 accumulation and constitutive expression of NRF2 target genes, many of which are at the interface between antioxidant function and anabolic processes that support cellular proliferation. Nrf2 activation promotes lung tumor initiation and early progression in murine models of lung cancer, but which Nrf2 targets mediate these phenotypes is unknown. Nrf2 regulates two parallel antioxidant systems mediated by thioredoxin reductase 1 (TXNRD1) and glutathione reductase (GSR), which promote the reduction of protein antioxidant thioredoxin (TXN) and tripeptide antioxidant glutathione (GSH), respectively. We deleted TXNRD1 and G

SUBMITTER: Sherwood AM 

PROVIDER: S-EPMC12133717 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature