ArticleCancer research2023
Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- Txnrd2 loss in skeletal muscle causes muscle atrophy and drives leanness and obesity resistance.Redox biology · 2026Article
- A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification.Redox biology · 2026Review
- Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.The EMBO journal · 2026Article
- NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions.Nature metabolism · 2026Article
- Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells.Nature metabolism · 2026Article
- A hormetic transcriptional program coregulates invasion, proliferation and dormancy to define metastatic potential.Nature communications · 2026Article
- Mangiferin in human disease: Multifaceted mechanisms and applications (Review).International journal of molecular medicine · 2026Review
- Druggable genome CRISPR screening identifies the KEAP1/NRF2 axis as a mediator of PD-L1 expression.Communications biology · 2025Article
- Nrf2 Drives Epigenetic Reprogramming and Acts as the Master Regulator of KLF4 Expression and Activity in Arsenic-Induced Transformation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting.Oncogene · 2025Review
- Nrf2 Hyperactivation as a Driver of Radiotherapy Resistance and Suppressed Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- NRF2 activation in cancer and overview of NRF2 small molecule inhibitors.Archives of pharmacal research · 2025Review
- Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.Redox biology · 2025Article
- Targeting mitochondrial ribosomal protein expression by andrographolide and melatonin for colon cancer treatment.Cancer letters · 2025Article
- Dual Role of NRF2 in Pancreatic Precursor Lesions.Cancer research communications · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- The Role of Redox Environment in Tumors.Current medicinal chemistry · 2025Review
- Kelch-like ECH-associated Protein 1/Nuclear Factor Erythroid 2-related Factor 2 Pathway and Its Interplay with Oncogenes in Lung Tumorigenesis.Journal of cancer prevention · 2024Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the KEAP1-NRF2 (Kelch-like ECH-associated protein 1-nuclear factor-erythroid 2 p45-related factor 2) pathway occur in up to a third of non-small cell lung cancer (NSCLC) cases and often confer resistance to therapy and poor outcomes. Here, we developed murine alleles of the KEAP1 and NRF2 mutations found in human NSCLC and comprehensively interrogated their impact on tumor initiation and progression. Chronic NRF2 stabilization by Keap1 or Nrf2 mutation was not sufficient to induce tumorigenesis, even in the absence of tumor suppressors, p53 or LKB1. When combined with KrasG12D/+, constitutive NRF2 activation promoted lung tumor initiation and early progression of hyperplasia to low-grade tumors but impaired their progression to advanced-grade tumors, which was reversed by NRF2 deletion. Finally, NRF2 overexpression in KEAP1 mutant human NSCLC cell lines was detrimental to cell proliferation, viability, and anchorage-independent colony formation. Collectively, these results establish the context-dependence and activity threshold for NRF2 during the lung tumorigenic process. SIGNIFICANCE: Stabilization of the transcription factor NRF2 promotes oncogene-driven tumor initiation but blocks tumor progression, indicating distinct, threshold-dependent effects of the KEAP1/NRF2 pathway in different stages of lung tumorigenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.