ArticleNature communications2021
STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Identification of STAT1 as a biomarker for lymph node metastasis in esophageal squamous cell carcinoma.Journal of molecular histology · 2026Article
- GRWD1 as a Novel Signature and It Down Regulates IFN in Skin Aging.Cell biochemistry and function · 2026Article
- Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics.eLife · 2026Article
- A feedback mechanism from prostate cancer cells to macrophages, reinforced by STAT1, regulates tumor progression and resistance to radiotherapy.Cell death & disease · 2026Article
- Succinate dehydrogenase-deficient cancer cells have increased susceptibility to Ym155-induced DNA damage.Endocrine-related cancer · 2026Article
- Ultrasound-activated and P-selectin-targeted liposomes overcome biofilm barriers for surgical site infections therapy.Journal of nanobiotechnology · 2025Article
- The dual impact of oxidative stress on breast cancer.Scientific reports · 2025Article
- Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.Science advances · 2025Article
- STAT1 increases the sensitivity of lung adenocarcinoma to carbon ion irradiation via HO-1-mediated ferroptosis.Molecular and cellular biochemistry · 2025Article
- M1 Macrophage is a Novel Potential Trigger for Endothelial Senescence: Role of Exosomal miR-155 Targeting SOCS1 Signal.Human mutation · 2025Article
- S1PR1 suppresses lung adenocarcinoma progression through p-STAT1/miR-30c-5 p/FOXA1 pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.Clinical proteomics · 2024Article
- TNIP3 protects against pathological cardiac hypertrophy by stabilizing STAT1.Cell death & disease · 2024Article
- Machine learning-based identification of novel hub genes associated with oxidative stress in lupus nephritis: implications for diagnosis and therapeutic targets.Lupus science & medicine · 2024Article
- Unveiling the Nexus: Cellular Metabolomics Unravels the Impact of Estrogen on Nicotinamide Metabolism in Mitigating Rheumatoid Arthritis Pathogenesis.Metabolites · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
- ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.Gland surgery · 2024Article
- High-dose ascorbic acid potentiates immune modulation through STAT1 phosphorylation inhibition and negative regulation of PD-L1 in experimental sepsis.Inflammopharmacology · 2024Article
- An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition.RSC chemical biology · 2023Article
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 1 country.
Funding
Abstract
Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.
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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.