C/EBPβ promotes the expression of atrophy‐inducing factors by tumours and is a central regulator of cancer cachexia

Autor: Hamood AlSudais, Rashida Rajgara, Aisha Saleh, Nadine Wiper‐Bergeron
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 13, Iss 1, Pp 743-757 (2022)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12909
Popis: Abstract Background CCAAT/enhancer‐binding protein β (C/EBPβ) is a transcription factor whose high expression in human cancers is associated with tumour aggressiveness and poor outcomes. Most advanced cancer patients will develop cachexia, characterized by loss of skeletal muscle mass. In response to secreted factors from cachexia‐inducing tumours, C/EBPβ is stimulated in muscle, leading to both myofibre atrophy and the inhibition of muscle regeneration. Involved in the regulation of immune responses, C/EBPβ induces the expression of many secreted factors, including cytokines. Because tumour‐secreted factors drive cachexia and aggressive tumours have higher expression of C/EBPβ, we examined a potential role for C/EBPβ in the expression of tumour‐derived cachexia‐inducing factors. Methods We used gain‐of‐function and loss‐of‐function approaches in vitro and in vivo to evaluate the role of tumour C/EBPβ expression on the secretion of cachexia‐inducing factors. Results We report that C/EBPβ overexpression up‐regulates the expression of 260 secreted protein genes, resulting in a secretome that inhibits myogenic differentiation (−31%, P
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