{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:28:22Z","timestamp":1771306102270,"version":"3.50.1"},"reference-count":69,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA024284"],"award-info":[{"award-number":["AA024284"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic alcohol consumption enhances cancer\u2010associated cachexia, which is one of the major causes of decreased survival. The precise molecular mechanism of how alcohol consumption enhances cancer\u2010associated cachexia, especially skeletal muscle loss, remains to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a mouse model of chronic alcohol consumption, in which 20% (w\/v) alcohol was provided as sole drinking fluid, and Lewis lung carcinoma to study the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that alcohol consumption up\u2010regulated the expression of MAFbx, MuRF\u20101, and LC3 in skeletal muscle, suggesting that alcohol\u00a0enhanced ubiquitin\u2010mediated proteolysis and LC3\u2010mediated autophagy. Alcohol consumption enhanced phosphorylation of Smad2\/3, p38, and ERK and decreased the phosphorylation of FOXO1. These are the signaling molecules governing protein degradation pathways. Moreover, alcohol consumption slightly up\u2010regulated the expression of insulin receptor substrate\u20101, did not affect phosphatidylinositol\u20103 kinase, but decreased the phosphorylation of Akt and mammalian target of rapamycin (mTOR), and down\u2010regulated the expression of Raptor and p70 ribosomal kinase S6 kinase, suggesting that alcohol impaired protein synthesis signaling pathway in skeletal muscle of tumor\u2010bearing mice. Alcohol consumption enhanced the expression of myostatin in skeletal muscle, plasma, and tumor, but did not affect the expression of myostatin in non\u2013tumor\u2010bearing mice. In TNF\u03b1 knockout mice, the effects of alcohol\u2010enhanced expression of myostatin and protein degradation\u2010related signaling molecules, and decreased protein synthesis signaling in skeletal muscle were abolished. Consequently, alcohol consumption neither affected cancer\u2010associated cachexia nor decreased the survival of TNF\u03b1 KO mice bearing cachectic cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chronic alcohol consumption enhances cancer\u2010associated skeletal muscle loss through suppressing Akt\/mTOR\u2010mediated protein synthesis pathway and enhancing protein degradation pathways. This process is initiated by TNF\u03b1 and mediated by myostatin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14221","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T12:25:15Z","timestamp":1572265515000},"page":"66-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chronic Alcohol Consumption Enhances Skeletal Muscle Wasting in Mice Bearing Cachectic Cancers: The Role of TNF\u03b1\/Myostatin Axis"],"prefix":"10.1111","volume":"44","author":[{"given":"Yuanfei","family":"Li","sequence":"first","affiliation":[{"name":"From the Department of Pharmaceutical Sciences (YL, FZ, SM, AL, HZ) College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"},{"name":"Department of Oncology (YL) The First Hospital of Shanxi Medical University Taiyuan 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