ArticleAmerican journal of physiology. Endocrinology and metabolism2012
JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 312 papers, 1 of them a synthesis that pooled it.
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Who cites it
312 citing papers in PubMed, 1 synthesis or guideline pooled it, 438 citations in OpenAlex.
- Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.Life science alliance · 2024Trial
- Targeting host ferroptosis in cancer cachexia: Tumor-immune triggers, tissue wasting, and the therapeutic paradox.iScience · 2026Review
- Emerging roles of OSM and EDA2R-NIK signalling in cancer-associated muscle wasting.Journal of muscle research and cell motility · 2026Review
- Circulating MicroRNAs Reflect Systemic Inflammation and Metabolic Dysfunction in Oesophageal Squamous Cell Carcinoma-Associated Cachexia.Journal of cachexia, sarcopenia and muscle · 2026Article
- Circulating granulocyte colony-stimulating factor as a sex-unbiased global marker of lung and colorectal cancer cachexia pre-clinical models.Experimental physiology · 2026Article
- Multi-organ transcriptome profiling in an isogenic cachexia-inducing xenograft model to dissect host responses across heart, liver, kidney, and muscle.Human cell · 2026Article
- Understanding cachexia and muscle dysfunction in the context of metastatic breast cancer.Cancer metastasis reviews · 2026Review
- Tuberculosis and Cellular Metabolism: Insights into the Crosstalk Between Macrophage Immunometabolism and Muscle Dysregulation.International journal of molecular sciences · 2026Review
- Prevalence and prognostic impact of cancer cachexia in patients with bladder cancer: a multicenter retrospective study.International journal of clinical oncology · 2026Article
- Li-ginseng powder alleviates cancer cachexia in mice by regulating the ubiquitin-proteasome pathway and reducing inflammation.Journal of ginseng research · 2026Article
- A Drosophila tumor model identifies a conserved Upd-JAK/STAT-Akh signaling axis associated with metabolic changes in cancer cachexia.Disease models & mechanisms · 2026Article
- Bilateral versus unilateral injection of Lewis lung carcinoma cells in female mice fed a Western diet: effects on cachexia severity, tumor burden, and tumor ulcerations.BMC research notes · 2026Article
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Formation of Liver Metastases Is Accompanied by Accelerated Musculoskeletal Deficits in LLC Tumor Hosts.International journal of molecular sciences · 2026Article
- Cancer cachexia: A tumor-driven disorder of whole-body homeostasis.Cancer cell · 2026Review
- Cancer cachexia induces senescent reprogramming of brown adipose tissue and pro-cachectic S100A9 secretion by adipocytes.Cell death & disease · 2026Article
- Tumor-muscle communication in cancer-associated cachexia (Review).Oncology letters · 2026Review
- The Conjugated Bile Acids Profile Suggests a Novel Liver-Muscle Axis Associated With Sarcopenia in Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Phloretin Attenuates Cancer Cachexia-Induced Skeletal Muscle Wasting Associated with the Modulation of STAT3 Signaling.Biomedicines · 2026Article
252 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C(2)C(12) myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia.
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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.