{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:45:04Z","timestamp":1793414704035,"version":"4.5.0"},"reference-count":120,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012948","name":"Minist\u00e8re de l'Enseignement sup\u00e9rieur, de la Recherche et de l'Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancer cachexia is a systemic hypoanabolic and catabolic syndrome that diminishes the quality of life of cancer patients, decreases the efficiency of therapeutic strategies and ultimately contributes to decrease their lifespan. The depletion of skeletal muscle compartment, which represents the primary site of protein loss during cancer cachexia, is of very poor prognostic in cancer patients. In this review, we provide an extensive and comparative analysis of the molecular mechanisms involved in the regulation of skeletal muscle mass in human cachectic cancer patients and in animal models of cancer cachexia. We summarize data from preclinical and clinical studies investigating how the protein turnover is regulated in cachectic skeletal muscle and question to what extent the transcriptional and translational capacities, as well as the proteolytic capacity (ubiquitin\u2013proteasome system, autophagy\u2013lysosome system and calpains) of skeletal muscle are involved in the cachectic syndrome in human and animals. We also wonder how regulatory mechanisms such as insulin\/IGF1\u2013AKT\u2013mTOR pathway, endoplasmic reticulum stress and unfolded protein response, oxidative stress, inflammation (cytokines and downstream IL1\u00df\/TNF\u03b1\u2013NF\u2010\u03baB and IL6\u2013JAK\u2013STAT3 pathways), TGF\u2010\u00df signalling pathways (myostatin\/activin A\u2010SMAD2\/3 and BMP\u2010SMAD1\/5\/8 pathways), as well as glucocorticoid signalling, modulate skeletal muscle proteostasis in cachectic cancer patients and animals. Finally, a brief description of the effects of various therapeutic strategies in preclinical models is also provided. Differences in the molecular and biochemical responses of skeletal muscle to cancer cachexia between human and animals (protein turnover rates, regulation of ubiquitin\u2010proteasome system and myostatin\/activin A\u2010SMAD2\/3 signalling pathways) are highlighted and discussed. Identifying the various and intertwined mechanisms that are deregulated during cancer cachexia and understanding why they are decontrolled will provide therapeutic targets for the treatment of skeletal muscle wasting in cancer patients.<\/jats:p>","DOI":"10.1002\/jcsm.13073","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T06:45:24Z","timestamp":1677825924000},"page":"1150-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Molecular mechanisms of cancer cachexia\u2010related loss of skeletal muscle mass: data analysis from preclinical and clinical studies"],"prefix":"10.1002","volume":"14","author":[{"given":"Agn\u00e8s","family":"Martin","sequence":"first","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 EA 7424, Univ Lyon Universit\u00e9 Jean Monnet Saint\u2010Etienne  Saint\u2010Priest\u2010en\u2010Jarez France"},{"name":"Share first authorship."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann S.","family":"Gallot","sequence":"additional","affiliation":[{"name":"LBEPS, Univ Evry, IRBA, Universit\u00e9 Paris Saclay  Evry France"},{"name":"Share first authorship."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-8207","authenticated-orcid":false,"given":"Damien","family":"Freyssenet","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 EA 7424, Univ Lyon Universit\u00e9 Jean Monnet Saint\u2010Etienne  Saint\u2010Priest\u2010en\u2010Jarez France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.105"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(81)90145-1"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4318"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.060228"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0123-0"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12529"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12402"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.289.6445.584"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980101)82:1<42::AID-CNCR5>3.0.CO;2-M"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.045708"},{"key":"e_1_2_16_13_1","first-page":"4807","article-title":"Efflux of 3\u2010methylhistidine from the leg in cancer patients who experience weight loss","volume":"42","author":"Lundholm K","year":"1982","journal-title":"Cancer Res"},{"key":"e_1_2_16_14_1","first-page":"37","article-title":"Leucine kinetics in patients with benign disease, non\u2010weight\u2010losing cancer, and cancer cachexia: studies at the whole\u2010body and tissue level and the response to nutritional support","volume":"109","author":"Shaw JH","year":"1991","journal-title":"Surgery"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2004"},{"key":"e_1_2_16_16_1","first-page":"6089","article-title":"Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover","volume":"51","author":"Beck SA","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_16_17_1","first-page":"2779","article-title":"Protein synthesis measured in vivo in muscle and liver of cachectic tumor\u2010bearing mice","volume":"44","author":"Emery PW","year":"1984","journal-title":"Cancer Res"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1993.126"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024650"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.1.R133"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1995.268.5.E996"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12310"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116897"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117929"},{"key":"e_1_2_16_25_1","first-page":"5568","article-title":"Increased ATP\u2010ubiquitin\u2010dependent proteolysis in skeletal muscles of tumor\u2010bearing rats","volume":"54","author":"Temparis S","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1479"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2990071"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24611"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602780"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.592"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091264"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00121.2011"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0425"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12550"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-997"},{"key":"e_1_2_16_36_1","first-page":"161","article-title":"Pathological changes in voluntary muscles in general diseases","volume":"5","author":"Jewesbury RC","year":"1912","journal-title":"Proc R Soc Med"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.11.006"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pky043"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68523"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00778.2005"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.4109"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0057"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002257R"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay9592"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.016"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2133"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23798"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.058388"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23945"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12005"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2016.06.003"},{"key":"e_1_2_16_52_1","first-page":"257","article-title":"Systemic inflammation correlates with increased expression of skeletal muscle ubiquitin but not uncoupling proteins in cancer cachexia","volume":"14","author":"DeJong CH","year":"2005","journal-title":"Oncol Rep"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-31-81"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.10.017"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs1020353"},{"key":"e_1_2_16_56_1","first-page":"15","article-title":"Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia","volume":"27","author":"Constantinou C","year":"2011","journal-title":"Int J Mol Med"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00104.2006"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.10.004"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00057.2013"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420174"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111020"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-230375"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-011-0049-z"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21798"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-012-0071-9"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.11.003"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46178-9"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12225"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26991"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-189977"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.412606"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010003"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-014-0141-2"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0054-2"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4976"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.011"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12642"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.12.023"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0610com"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.05.032"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12031"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00726-x"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12271"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12554"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)80290-4"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1299"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714703115"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022538"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087776"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910610123"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30340"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11030285"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3600143"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12678"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12232"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00300.2010"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0177-2"},{"key":"e_1_2_16_98_1","first-page":"1078","article-title":"Cachectic skeletal muscle response to a novel bout of low\u2010frequency stimulation","volume":"2014","author":"Puppa MJ","year":"1985","journal-title":"J Appl Physiol"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12138"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.02.017"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2818"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-019-09510-4"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC352_5"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600466"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12033"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12077"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3152"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00716.2007"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01645-7"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.437"},{"key":"e_1_2_16_111_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1500"},{"key":"e_1_2_16_112_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0959"},{"key":"e_1_2_16_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11440-5"},{"key":"e_1_2_16_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.123"},{"key":"e_1_2_16_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2019.10.013"},{"key":"e_1_2_16_116_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.8817"},{"key":"e_1_2_16_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.05.026"},{"key":"e_1_2_16_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.10.010"},{"key":"e_1_2_16_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(95)04026-9"},{"key":"e_1_2_16_120_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12939"},{"key":"e_1_2_16_121_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013591"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13073","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.13073","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T04:07:56Z","timestamp":1703822876000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":120,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/jcsm.13073"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13073","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]},"assertion":[{"value":"2021-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}