title: Autophagy is induced in the skeletal muscle of cachectic cancer patients.
abstract: Basal rates of autophagy can be markedly accelerated by environmental stresses. Recently, autophagy has been involved in cancer-induced muscle wasting. Aim of this study has been to evaluate if autophagy is induced in the skeletal muscle of cancer patients. The expression (mRNA and protein) of autophagic markers has been evaluated in intraoperative muscle biopsies. Beclin-1 protein levels were increased in cachectic cancer patients, suggesting autophagy induction. LC3B-I protein levels were not significantly modified. LC3B-II protein levels were significantly increased in cachectic cancer patients suggesting either increased autophagosome formation or reduced autophagosome turnover. Conversely, p62 protein levels were increased in cachectic and non-cachectic cancer patients, suggesting impaired autophagosome clearance. As for mitophagy, both Bnip3 and Nix/Bnip3L show a trend to increase in cachectic patients. In the same patients, Parkin levels significantly increased, while PINK1 was unchanged. At gene level, Beclin-1, p-62, BNIP3, NIX/BNIP3L and TFEB mRNAs were not significantly modulated, while LC3B and PINK1 mRNA levels were increased and decreased, respectively, in cachectic cancer patients. Autophagy is induced in the skeletal muscle of cachectic cancer patients, although autophagosome clearance appears to be impaired. Further studies should evaluate whether modulation of autophagy could represent a relevant therapeutic strategy in cancer cachexia.
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Zaira
authors.initials: Z
authors.lastname: Aversa
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.|Interuniversity Institute of Myology, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pin
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Lucia
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.|Interuniversity Institute of Myology, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Penna
authors.affiliation: Department of Surgery, M.G. Vannini Hospital, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Verzaro
authors.affiliation: Department of Surgery, M.G. Vannini Hospital, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fazi
authors.affiliation: UOSA Chirurgia Bariatrica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Colasante
authors.affiliation: UOSA Chirurgia Bariatrica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tirone
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi Fanelli
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Ramaccini
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.|Interuniversity Institute of Myology, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Costelli
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muscaritoli
mesh_terms: D000368:Aged; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071186:Beclin-1; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000099202:PTEN-Induced Putative Kinase; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; C502070:MAP1LC3B protein, human