ArticleNature communications2017
NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review.Aging and disease · 2024Pooled it
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Small Interfering RNA (siRNA) as a Targeted Therapy for Acute Respiratory Distress Syndrome: Evidence from Experimental Models.International journal of molecular sciences · 2026Review
- Magnetically-Induced Suppression of Oxidative Stress Prevents Venous Thrombosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of NADPH Oxidase 4 in Neutrophil-Mediated Immune Escape in Gastric Cancer.International journal of biological sciences · 2026Article
- Genetic and Pharmacological Inhibition of NOX4 Protects Against Rhabdomyolysis-Induced Acute Kidney Injury Through Suppression of Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- NADPH oxidase 1/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts.Signal transduction and targeted therapy · 2025Article
- Enhancing Selectivity and Potency of SJournal of medicinal chemistry · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
- NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses.Scientific reports · 2025Article
- Nitazoxanide Modulates Mitochondrial Function and Inflammatory Metabolism in Chondrocytes from Patients with Osteoarthritis via AMPK/mTORC1 Signaling.Antioxidants (Basel, Switzerland) · 2025Article
- Warburg effect and lactylation in cancer: mechanisms for chemoresistance.Molecular medicine (Cambridge, Mass.) · 2025Review
- The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization.International journal of molecular sciences · 2025Review
- The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.Frontiers in cell and developmental biology · 2025Review
- Anti-Inflammatory and Anticancer Effects of Kaurenoic Acid in Overcoming Radioresistance in Breast Cancer Radiotherapy.Nutrients · 2024Article
- Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation.Redox biology · 2024Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2). Finally, we show that NOX4 silencing, through PKM2, sensitizes cultured and ex vivo freshly isolated human-renal carcinoma cells to drug-induced cell death in xenograft models and ex vivo cultures. These findings highlight yet unidentified insights into the molecular events driving cancer evasive resistance and suggest modulation of ATP levels together with cytotoxic drugs could overcome drug-resistance in glycolytic cancers.
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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.