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Levels of IL\u20106 cytokine family members are increased during cancer\u2010related cachexia and induce intracellular signaling through glycoprotein130 (gp130). Although muscle STAT3 and circulating IL\u20106 are implicated in cancer\u2010induced muscle wasting, there is limited understanding of muscle gp130's role in this process. Therefore, we investigated the role of skeletal muscle gp130 (skm\u2010gp130) in cancer\u2010induced alterations in the regulation of muscle protein turnover. Lewis lung carcinoma (LLC) cells were injected into 8\u2010wk\u2010old skmgp130\u2010knockout (KO) mice or wild\u2010type mice. Skeletal muscle loss was attenuated by 16% in gp130\u2010KO mice, which coincided with attenuated LLC\u2010induced phosphorylation of muscle STAT3, p38, and FOXO3. gp130 KO did not restore mTOR inhibition or alter AMP\u2010activated protein kinase (AMPK) expression. The induction of atrogin expression and p38 phosphorylation in C2C12 myotubes exposed to LLC\u2010treated medium was attenuated by gp130 inhibition, but mTOR inhibition was not restored. STAT signaling inhibition in LLC\u2010treated myotubes did not attenuate the induction of p38 or AMPK phosphorylation. We concluded that, during LLC\u2010induced cachexia, skm\u2010gp130 regulates muscle mass signaling through STAT3 and p38 for the activation of FOXO3 and atrogin, but does not directly regulate the suppression of mTOR.\u2014Puppa, M. J., Gao, S., Narsale, A. A., Carson, J. A. Skeletal muscle glycoprotein 130's role in Lewis lung carcinoma\u2013induced cachexia.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 998\u20131009 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-240580","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T22:57:09Z","timestamp":1382396229000},"page":"998-1009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Skeletal muscle glycoprotein 130's role in Lewis lung carcinoma\u2013induced cachexia"],"prefix":"10.1096","volume":"28","author":[{"given":"Melissa J.","family":"Puppa","sequence":"first","affiliation":[{"name":"Integrative Muscle Biology Laboratory Department of Exercise Science University of South Carolina Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory Department of Exercise Science University of South Carolina Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi A.","family":"Narsale","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory Department of Exercise Science University of South Carolina Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Carson","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory Department of Exercise Science University of South Carolina Columbia South Carolina USA"},{"name":"Center for Colon Cancer Research University of South Carolina Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2008.06.013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2009.12.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7117.1219"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc927"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mco.0000078983.18774.cc"},{"key":"e_1_2_7_9_1","first-page":"1521","article-title":"Pro\u2010inflammatory cytokines and oxidative stress\/antioxidant parameters characterize the bio\u2010humoral profile of early cachexia in lung cancer patients","volume":"18","author":"Fortunati N.","year":"2007","journal-title":"Oncol. 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