Cited by 357Muscle Physiology and DisordersNutrition and Health in AgingCytokine Signaling Pathways and Interactions

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STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

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Bonetto, Andrea, Aydogdu, Tufan, Kunzevitzky, Noelia, Guttridge, Denis C., Khuri, Sawsan, Koniaris, Leonidas G., Zimmers, Teresa A.·2011·PLoS ONE

DOI 10.1371/journal.pone.0022538PMC PMC3140523

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Abstract

BACKGROUND: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia. METHODOLOGY/PRINCIPAL FINDINGS: Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer. CONCLUSIONS/SIGNIFICANCE: These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such that amino acids liberated by increased proteolysis in cachexia are synthesized into acute phase proteins and exported into the blood.

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Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190
Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · cited 1×
“STAT3 is activated in part by phosphorylation at Y705, which induces dimerization, nuclear translocation and DNA binding [51,52].”
Background
Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member
McPherron, A. C., Lawler, A. M., & Lee, S.-J. (1997) · Nature · doi:10.1038/387083a0 · Cited by 4,013
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521
Stat3 as an Oncogene
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells
Chen, X., Han, X., Yuan, P., Fang, F., Huss, M., Vega, V. B., Wong, E., Orlov, Y. L., Zhang, W., Jiang, J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.04.043 · Cited by 2,547
Cachexia: a new definition.
Evans, W., Morley, J., Argilés, J., Bales, C., Baracos, V., Guttridge, D., Jatoi, A., Kalantar-zadeh, K., Lochs, H., Mantovani, G., et al. (2008) · Clinical Nutrition · doi:10.1016/j.clnu.2008.06.013 · Cited by 2,341
The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors.
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964
Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251541198 · Cited by 1,774

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Show all 84 references

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JR Libonati, 2001, Brief muscle hypoperfusion/hyperemia: an ergogenic aid?, J Strength Cond Res, 15, 362

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Items 101–200 of 357

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Lee, S.-R., Khamoui, A. V., Jo, E., Park, B., Zourdos, M. C., Panton, L. B., Ormsbee, M. J., & Kim, J. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0316-5 · Cited by 60
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Abid, H., Ryan, Z. C., Delmotte, P. F., Sieck, G. C., & Lanza, I. R. (2020) · The FASEB Journal · doi:10.1096/fj.202000965rr · Cited by 60
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Der‐Torossian, H., Wysong, A. S., Shadfar, S., Willis, M. S., McDunn, J. E., & Couch, M. E. (2013) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-012-0101-7 · Cited by 56
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Blackwell, T. A., Červenka, I., Khatri, B., Brown, J. L., Rosa‐Caldwell, M. E., Lee, D. E., Perry, R. A., Brown, L. A., Haynie, W. S., Wiggs, M. P., et al. (2018) · Physiological Genomics · doi:10.1152/physiolgenomics.00061.2018 · Cited by 56
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Judge, S. M., Deyhle, M. R., Neyroud, D., Nosacka, R. L., D’Lugos, A. C., Cameron, M. E., Vohra, R., Smuder, A. J., Roberts, B. M., Callaway, C. S., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-1558 · Cited by 52
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Mubaid, S., Ma, J. F., Omer, A., Ashour, K., Lian, X. J., Sánchez, B. J., Robinson, S., Cammas, A., Dormoy-Raclet, V., Marco, S. D., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905172116 · Cited by 53
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Laine, A. M., Iyengar, P., & Pandita, T. K. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0189 · Cited by 51
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Pretto, F., Ghilardi, C., Moschetta, M., Bassi, A. L., Rovida, A., Scarlato, V., Talamini, L., Fiordaliso, F., Bisighini, C., Damia, G. L. M., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2812 · Cited by 48
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Freire, P. P., Fernández, G. J., Cury, S. S., de Moraes, D., Oliveira, J. S., de Oliveira, G., Dal‐Pai‐Silva, M., Reis, P. P., & Carvalho, R. F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081962 · Cited by 45
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Zhang, L., Chen, Z., Wang, Y., Tweardy, D. J., & Mitch, W. E. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00480.2019 · Cited by 47
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Wyart, E., Bindels, L. B., Mina, E., Menga, A., Stanga, S., & Porporato, P. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228592 · Cited by 51
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Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46
Rel A/p65 is required for cytokine-induced myotube atrophy
Yamaki, T., Wu, C., Gustin, M., Lim, J. K., Jackman, R. W., & Kandarian, S. C. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00111.2012 · Cited by 46
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Little, R. D., Prieto‐Potín, I., Pérez-Baos, S., Villalvilla, A., Gratal, P., Cicuttini, F., Largo, R., & Herrero‐Beaumont, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-06581-6 · Cited by 44
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Self-citation
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Self-citation
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Jiang, F., Zhang, Z., Zhang, Y., WU, J., Yu, L., & Liu, S. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4639 · Cited by 41
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Self-citation
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Graça, F. A., Rai, M., Hunt, L. C., Stephan, A., Wang, Y., Gordon, B., Wang, R., Quarato, G., Xu, B., Fan, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30120-1 · Cited by 41
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Robert, F., Mills, J. R., Agenor, A., Wang, D., Marco, S. D., Cencic, R., Tremblay, M. L., Gallouzi, I., Hekimi, S., Wing, S. S., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-2739 · Cited by 39
Ovarian function's role during cancer cachexia progression in the female mouse.
Hetzler, K. L., Hardee, J., LaVoie, H. A., Murphy, E. A., & Carson, J. (2017) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00294.2016 · Cited by 35
Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia
Shum, A. M. Y., Fung, D. C. Y., Corley, S., McGill, M. C., Bentley, N. L., Tan, T. C., Wilkins, M. R., & Polly, P. (2015) · Physiological Genomics · doi:10.1152/physiolgenomics.00128.2014 · Cited by 38
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O’Connell, T. M., Golzarri‐Arroyo, L., Pin, F., Barreto, R., Dickinson, S., Couch, M. E., & Bonetto, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.720096 · Cited by 37
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Self-citation
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Johns, N., Tan, B. H. L., Macmillan, M. T., Solheim, T. S., Ross, J. A. F., Baracos, V. E., Damaraju, S., & Fearon, K. C. H. (2014) · Journal of Genetics · doi:10.1007/s12041-014-0405-9 · Cited by 30
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Authors: Bonetto, A., Aydogdu, T., Kunzevitzky, N., Guttridge, D. C., Khuri, S., Koniaris, L. G., & Zimmers, T. A.
Affiliations: University of Miami (US)
Corresponding author: Zimmers, Teresa A.
ORCID: Bonetto, Andrea
Kunzevitzky, Noelia
Khuri, Sawsan
Koniaris, Leonidas G.
Zimmers, Teresa A.
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2011-07-20
Volume: 6
Issue: 7
Pages: e22538
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0022538
PMC: PMC3140523
OpenAlex: W2052712443
Cited by: 348
References: 84
Citations by year: 2026: 17 · 2025: 24 · 2024: 16 · 2023: 21 · 2022: 17 · 2021: 30 · 2020: 38 · 2019: 28 · 2018: 38 · 2017: 23 · 2016: 20 · 2015: 21 · 2014: 23 · 2013: 19 · 2012: 11
FWCI: 7.15
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: U.S. Department of Defense
American Cancer Society
University of Miami
National Cancer Institute (CA122596, R01CA122596)
National Institute of General Medical Sciences (R01GM092758)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: cancer cachexia, STAT3 signaling, skeletal muscle atrophy, interleukin-6, acute phase response, acute phase proteins, fibrinogen, serum amyloid A, SOCS3, C26 colon carcinoma, muscle protein degradation, muscle transcriptome, IL-6 family cytokines
MeSH terms: Acute-Phase Reaction, Animals, Cachexia, Colonic Neoplasms, Female, Humans, Liver, Gene Expression Regulation, Neoplastic, Cytokines, Muscle, Skeletal, Cell Line, Tumor, STAT3 Transcription Factor, Mice, Transcriptome

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STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

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