ArticleNature communications2024
PPIA dictates NRF2 stability to promote lung cancer progression.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dietary sulforaphane in cancer chemoprevention: epigenetic regulation and PRMT5-MEP50 complex inhibition-a systematic review.Frontiers in pharmacology · 2026Pooled it
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- Salvianolic acid B suppresses non-small cell lung cancer growth by promoting Nrf2 proteasomal degradation and triggering autophagy-dependent ferroptosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- PYCR1 promotes glutamine metabolism and the progression of lung adenocarcinoma by regulating the expression of OPLAH.Clinical and experimental medicine · 2026Article
- AI-Driven Combination Therapy for Counteracting Dysregulated Genes in Lung Adenocarcinoma: Contribution-Aware Metaheuristic for Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.Toxicological research · 2026Review
- Identification of prognostic biomarkers and immunotherapy response predictors in lung adenocarcinoma: integrative Mendelian randomization and machine learning analysis.Translational lung cancer research · 2026Article
- Context-dependent NRF2 signaling in cancer: mechanisms and precision modulation.Molecular biology reports · 2026Review
- The anticancer properties of dexmedetomidine in papillary thyroid cancer and its underlying mechanisms.Scientific reports · 2026Article
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- PPIA regulates fatty acid and glutamine metabolism in lung adenocarcinoma based on multiomics prognostic model and experiment validation.Scientific reports · 2026Article
- Hot-yet-suppressed under PD-1 blockade: an RMP-NRF2-PD-L1 axis associated with a reduced proportional response in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- CypA Mediates Non-Small Cell Lung Cancer Chemoresistance by Attenuating Ferroptosis via Stabilizing SLC7A11.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nrf2 as a redox checkpoint in autoimmune joint inflammation: microenvironmental redox control across the arthritis spectrum.Frontiers in immunology · 2026Review
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- Target agnostic cellular screening in the era of chemically induced proximity.RSC medicinal chemistry · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.
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What Socratic holds
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 Socratic graph.