ArticleMolecular oncology2021
Mitochondrial STAT3 regulates antioxidant gene expression through complex I-derived NAD in triple negative breast cancer.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention.Frontiers in endocrinology · 2023Pooled it
- IL-21 boosts T cell-therapy efficacy for solid tumors by enhancing mitochondrial Ca2+-mediated motility of effector CD8+ T cells.Cancer immunology research · 2026Article
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Synergistic anti-tumor activity of andrographolide and gemcitabine in intrahepatic cholangiocarcinoma through inhibition of RRM2 and the JAK/STAT3 pathway.Cancer chemotherapy and pharmacology · 2026Article
- IL-10-STAT3-Dependent Transcriptional Regulation in Microglia: Alzheimer's Disease and Neuroinflammation.Biomedicines · 2026Review
- Out of Nucleus: Serine 727 Phosphorylation Orchestrates Non-Canonical STAT3 Functions-Relevance to Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Bruton's tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax.Blood cancer journal · 2025Article
- Review
- The ubiquitin-specific protease 21 is critical for cancer cell mitochondrial function and regulates proliferation and migration.The Journal of biological chemistry · 2024Article
- Assessing Breast Cancer through Tumor Microenvironment Mapping of Collagen and Other Biomolecule Spectral Fingerprints─A Review.ACS sensors · 2024Review
- Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture.Chemosphere · 2024Article
- The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium.Frontiers in bioscience (Landmark edition) · 2024Review
- Construction of an oxidative stress-associated genes signature in breast cancer by machine learning algorithms.The Journal of international medical research · 2024Article
- Structural determinants of mitochondrial STAT3 targeting and function.Mitochondrial communications · 2024Article
- TAX1BP1 contributes to deoxypodophyllotoxin-induced glioma cell parthanatos via inducing nuclear translocation of AIF by activation of mitochondrial respiratory chain complex I.Acta pharmacologica Sinica · 2023Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma.MedComm · 2023Article
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with roles in inflammation and tumorigenicity. A fraction of STAT3 localizes in mitochondria, where it augments tumorigenesis via regulation of mitochondrial functions, including modulation of respiration and redox status. We show a novel mechanism for mitochondrial STAT3 regulation of redox homeostasis in triple-negative breast cancer cells. Loss of STAT3 diminished complex I dehydrogenase activity and impaired NAD+ regeneration, leading to impaired expression of glutathione biosynthetic genes and other antioxidant genes. Expressing mitochondrially restricted STAT3 or replenishment of the cellular NAD pool restored antioxidant gene expression, as did complementation of the NADH dehydrogenase activity by expression of the STAT3-independent yeast dehydrogenase, NDI1. These NAD-regulated processes contributed to malignant phenotypes by promoting clonal cell growth and migration. Proximity interaction and protein pull-down assays identified three components of complex I that associated with mitochondrial STAT3, providing a potential mechanistic basis for how mitochondrial STAT3 affects complex I activity. Our data document a novel mechanism through which mitochondrial STAT3 indirectly controls antioxidant gene regulation through a retrograde NAD+ signal that is modulated by complex I dehydrogenase activity.
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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.