title: Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia.
abstract: Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persistent expression of CCAAT/Enhancer Binding Protein beta (C/EBPβ) in muscle myoblasts. C/EBPβ is a bzip transcription factor that is expressed in muscle satellite cells and is normally downregulated upon differentiation. However, in myoblasts exposed to a cachectic milieu, C/EBPβ expression remains elevated, despite activation to differentiate, resulting in the inhibition of myogenin expression and myogenesis. In vivo, cancer cachexia results in increased number of Pax7+ cells that also express C/EBPβ and the inhibition of normal repair mechanisms. Loss of C/EBPβ expression in primary myoblasts rescues differentiation under cachectic conditions without restoring myotube size, indicating that C/EBPβ is an important inhibitor of myogenesis in cancer cachexia.
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Marchildon
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Émilie
authors.initials: É
authors.lastname: Lamarche
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Neena
authors.initials: N
authors.lastname: Lala-Tabbert
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: St-Louis
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Wiper-Bergeron
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002100:Cachexia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D017077:Culture Media, Conditioned