ArticleProceedings of the National Academy of Sciences of the United States of America2017
Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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
66 citing papers in PubMed.
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Review
- 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
- STAT3 inhibitor in oncology: a trial-based analysis of translational challenges and evolving therapeutic paradigms.Frontiers in oncology · 2026Article
- Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer.Cancer letters · 2025Article
- JAK2/STAT3 Signaling Pathway Modulates Acute Methylmercury Toxicity in the Mouse Astrocyte C8-D1A Cell Line.Neurochemical research · 2025Article
- Identification of STAT3 phosphorylation inhibitors using generative deep learning, virtual screening, molecular dynamics simulations, and biological evaluation for non-small cell lung cancer therapy.Molecular diversity · 2025Article
- Advances of signal transducer and activator of transcription 3 inhibitors in acute myeloid leukemia (Review).Oncology letters · 2025Review
- Review
- Key Role of STAT3 in Osteoarthritis: From Pathogenic Mechanisms to Targeted Therapy.International journal of nanomedicine · 2025Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- Role of STAT3 in cancer cell epithelial‑mesenchymal transition (Review).International journal of oncology · 2024Review
- HSF1 is involved in immunotherapeutic response through regulating APOJ/STAT3-mediated PD-L1 expression in hepatocellular carcinoma.Cancer biology & therapy · 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
- Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma.MedComm · 2023Article
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.Signal transduction and targeted therapy · 2023Review
- PARP inhibitors combined with radiotherapy: are we ready?Frontiers in pharmacology · 2023Review
- The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities.Cells · 2022Review
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
6 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
12 authors.
Funding
Abstract
In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The mSTAT3-drug interaction leads to mitochondrial dysfunction, accumulation of proteotoxic STAT3 aggregates, and cell death. The cytotoxic effects depend directly on the drug's ability to interfere with mSTAT3 and mitochondrial function, as demonstrated by site-directed mutagenesis and use of STAT3 knockout and mitochondria-depleted cells. Importantly, the lethal consequences of mSTAT3 inhibition are enhanced by glucose starvation and by increased reliance of cancer cells and tumor-initiating cells on mitochondria, resulting in potent activity in cell cultures and tumor xenografts in mice. These findings can be exploited for eliciting synthetic lethality in metabolically stressed cancer cells using high-affinity STAT3 inhibitors. Thus, this study provides insights on the role of mSTAT3 in cancer cells and a conceptual framework for developing more effective cancer therapies.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.