ArticleRedox biology2024
Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells.
Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- PSMA6 drives non-small cell lung cancer progression by stabilizing NEDD8 and activating NF-κB signaling.Translational lung cancer research · 2026Article
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- Context-dependent NRF2 signaling in cancer: mechanisms and precision modulation.Molecular biology reports · 2026Review
- Molecular Subtyping Based on EGFR Mutation-Associated Genes and the Prognostic Role of TRAF2 in Lung Adenocarcinoma.Human mutation · 2026Article
- TFAM Loss Induces Oxidative Stress and Divergent Phenotypes in Glioblastoma Metabolic Subtypes.International journal of molecular sciences · 2025Article
- Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species.Cells · 2025Article
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.Archives of pharmacal research · 2025Review
- Mechanisms underlying targeted mitochondrial therapy for programmed cardiac cell death.Frontiers in physiology · 2025Review
- The role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation.Frontiers in pharmacology · 2025Article
- Machine learning developed an immune evasion signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma.Frontiers in cell and developmental biology · 2025Article
- Unveiling the molecular blueprint of SKP-SCs-mediated tissue engineering-enhanced neuroregeneration.Journal of nanobiotechnology · 2024Article
- Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment.Archives of pharmacal research · 2024Article
- The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer.International journal of molecular sciences · 2024Review
- CircSpna2 attenuates cuproptosis by mediating ubiquitin ligase Keap1 to regulate the Nrf2-Atp7b signalling axis in depression after traumatic brain injury in a mouse model.Clinical and translational medicine · 2024Article
- Article
- Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.Biology direct · 2024Article
- Mass Spectrometry-Based Proteomics Technologies to Define Endogenous Protein-Protein Interactions and Their Applications to Cancer and Viral Infectious Diseases.Mass spectrometry reviewsReview
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Kelch-like ECH-associated protein 1 (KEAP1) - Nuclear factor erythroid 2 -related factor 2 (NRF2) pathway is the major transcriptional stress response system in cells against oxidative and electrophilic stress. NRF2 is frequently constitutively active in many cancers, rendering the cells resistant to chemo- and radiotherapy. Loss-of-function (LOF) mutations in the repressor protein KEAP1 are common in non-small cell lung cancer, particularly adenocarcinoma. While the mutations can occur throughout the gene, they are enriched in certain areas, indicating that these may have unique functional importance. In this study, we show that in the GSEA analysis of TCGA lung adenocarcinoma RNA-seq data, the KEAP1 mutations in R320 and R470 were associated with enhanced Tumor Necrosis Factor alpha (TNFα) - Nuclear Factor kappa subunit B (NFκB) signaling as well as MYC and MTORC1 pathways. To address the functional role of these hotspot mutations, affinity purification and mass spectrometry (AP-MS) analysis of wild type (wt) KEAP1 and its mutation forms, R320Q and R470C were employed to interrogate differences in the protein interactome. We identified TNF receptor associated factor 2 (TRAF2) as a putative protein interaction partner. Both mutant KEAP1 forms showed increased interaction with TRAF2 and other anti-apoptotic proteins, suggesting that apoptosis signalling could be affected by the protein interactions. A549 lung adenocarcinoma cells overexpressing mutant KEAP1 showed high TRAF2-mediated NFκB activity and increased protection against apoptosis, XIAP being one of the key proteins involved in anti-apoptotic signalling. To conclude, KEAP1 R320Q and R470C and its interaction with TRAF2 leads to activation of NFκB pathway, thereby protecting against apoptosis.
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