ArticleThe Journal of experimental medicine2020
SIRT1-NOX4 signaling axis regulates cancer cachexia.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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
50 citing papers in PubMed.
- Artificial Intelligence-Based Body Composition Analysis Reveals Sex-Specific Prognostic Markers and Their Clinical Value in Gastric Cancer: A Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Mechanistic interactions of diet, exercise, and pharmacotherapy in skeletal muscle metabolism: evidence and translational perspectives.Frontiers in physiology · 2026Review
- Skeletal muscle endothelial dysfunction through the activin A-PGC1α axis drives progression of cancer cachexia.Nature cancer · 2025Article
- Trigonelline attenuated sepsis-induced acute kidney injury by activating NAD+/SIRT1 Pathway.Physiological research · 2025Article
- Review
- Novel oral compound Z526 mitigates cancer-associated cachexia via intervening NF-κB signaling and oxidative stress.Genes & diseases · 2025Article
- Deciphering molecular crosstalk mechanisms between skeletal muscle atrophy and KRAS-mutant pancreatic cancer: a literature review.Hepatobiliary surgery and nutrition · 2025Review
- Bone Adaptations to a Whole Body Vibration Protocol in Murine Models of Different Ages: A Preliminary Study on Structural Changes and Biomarker Evaluation.Journal of functional morphology and kinesiology · 2025Article
- Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study.Frontiers in physiology · 2025Article
- Modulating mitochondria with natural extract compounds: from bench to clinical therapeutic opportunities for COPD.Frontiers in pharmacology · 2025Review
- Article
- Article
- Preventing loss of sirt1 lowers mitochondrial oxidative stress and preserves C2C12 myotube diameter in an in vitro model of cancer cachexia.Physiological reports · 2024Article
- Molecular Mechanisms of Cachexia: A Review.Cells · 2024Review
- DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive analysis of the prognostic, immunological, and diagnostic roles of SIRT1 in pan-cancer and its validation in KIRC.Frontiers in immunology · 2024Article
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Unlocking the Nexus of Sirtuins: A Comprehensive Review of Their Role in Skeletal Muscle Metabolism, Development, and Disorders.International journal of biological sciences · 2024Review
- Targeting Epigenetic Regulators with HDAC and BET Inhibitors to Modulate Muscle Wasting.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied. We observed a significant positive correlation between SIRT1 expression and muscle fiber cross-sectional area in pancreatic cancer patients. Rescuing Sirt1 expression by exogenous expression or pharmacological agents reverted cancer cell-induced myotube wasting in culture conditions and mouse models. RNA-seq and follow-up analyses showed cancer cell-mediated SIRT1 loss induced NF-κB signaling in cachectic muscles that enhanced the expression of FOXO transcription factors and NADPH oxidase 4 (Nox4), a key regulator of reactive oxygen species production. Additionally, we observed a negative correlation between NOX4 expression and skeletal muscle fiber cross-sectional area in pancreatic cancer patients. Knocking out Nox4 in skeletal muscles or pharmacological blockade of Nox4 activity abrogated tumor-induced cachexia in mice. Thus, we conclude that targeting the Sirt1-Nox4 axis in muscles is an effective therapeutic intervention for mitigating pancreatic cancer-induced cachexia.
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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.