The DOI matches its Crossref record; 78 of the 82 references it cites were found in a registry or an index.
The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse
Open accessAbstract
Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+) mouse is not known. Cachexia progression was studied in Apc(Min/+) mice that were either weight stable (WS) or had initial (≤5%), intermediate (6-19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.
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“The link between IL-6/STAT3 signaling and muscle and adipose tissue wasting is well established in mouse models of cachexia (White et al., 2011; Silva et al., 2015) and has been reinforced preliminarily in clinical studies.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as White et al., 2011
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4 of the 82 references couldn’t be matched to a known paper.
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Early Markers of Cardiac and Skeletal Muscle Metabolic Derangement in the Apc(min/+) Male Mouse
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Patient‐derived pancreatic tumour organoid implantation establishes novel pre‐cachexia mouse models
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Effects Of Exercise Training On Cachexia In Mice Bearing The Colon-26 Carcinoma
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Metadata
- Authors
- White, J. P., Baynes, J. W., Welle, S. L., Kostek, M. C., Matesic, L. E., Sato, S., & Carson, J. A.
- Affiliations
- University of South Carolina (US)
- University of Rochester Medicine (US)
- Corresponding author
- Carson, James A.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-09-19
- Volume
- 6
- Issue
- 9
- Pages
- e24650
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3176277
- OpenAlex
- W2151316758
- Cited by
- 260
- References
- 82
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 21 · 2023: 22 · 2022: 20 · 2021: 29 · 2020: 24 · 2019: 18 · 2018: 18 · 2017: 19 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 17 · 2012: 12
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Scholar Commons (University of South Carolina) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- Chugai Pharmaceutical
- National Cancer Institute (R01CA121249)
- National Center for Research Resources (P20RR017698)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- cancer cachexia, skeletal muscle protein turnover, muscle protein synthesis, muscle protein degradation, colorectal cancer, IL-6 signaling, AMPK, Raptor phosphorylation, muscle atrophy, weight loss, IL-6 receptor antibody
- MeSH terms
- Adenosine Triphosphate, Animals, Body Weight, Cachexia, Enzyme Activation, Inflammation, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Mice, Mutant Strains, Muscle Proteins, Myofibrils, Neoplasms, Organ Size, Phosphorylation, Protein Biosynthesis, Signal Transduction, Interleukin-6, Disease Progression, Muscle, Skeletal, Adiposity, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases, Proteolysis
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