{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:00:39Z","timestamp":1789992039249,"version":"4.0.1"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2016\/26169-0"],"award-info":[{"award-number":["2016\/26169-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["407360\/2018-2"],"award-info":[{"award-number":["407360\/2018-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt\/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-\u03b1. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt\/mTORC1 pathway and the eIF-2\u03b1 activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.<\/jats:p>","DOI":"10.3390\/cancers14010028","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2\u03b1 Modulation"],"prefix":"10.3390","volume":"14","author":[{"given":"Marcelo G.","family":"Pereira","sequence":"first","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"},{"name":"Leeds School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa A.","family":"Voltarelli","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"},{"name":"Sirio-Libanes Hospital, Sao Paulo 01308050, Brazil"},{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9488-2566","authenticated-orcid":false,"given":"Gabriel C.","family":"Tobias","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"},{"name":"Children\u2019s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children\u2019s Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"de Souza","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-9235","authenticated-orcid":false,"given":"Gabriela S.","family":"Borges","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-7319","authenticated-orcid":false,"given":"Ailma O.","family":"Paix\u00e3o","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ney R.","family":"de Almeida","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Scott","family":"Bowen","sequence":"additional","affiliation":[{"name":"Leeds School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilene","family":"Demasi","sequence":"additional","affiliation":[{"name":"Biochemistry and Biophysics Laboratory, Butantan Institute, Sao Paulo 05503900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen H.","family":"Miyabara","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-6506","authenticated-orcid":false,"given":"Patricia C.","family":"Brum","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.2147\/CMAR.S261585","article-title":"Cancer Cachexia: Definition, Staging, and Emerging Treatments","volume":"12","author":"Ni","year":"2020","journal-title":"Cancer Manag. 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