The 2015 ESPEN Sir David Cuthbertson lecture: Inflammation as the driving force of muscle wasting in cancer.
Alterations in amino acid protein metabolism are a key feature of the cancer cachexia syndrome. These changes -induced by both hormonal changes (that affect insulin sensitivity) and inflammatory mediators- are present in skeletal muscle influencing both, amino acid uptake and protein synthesis. In addition, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. Changes in the rate of myogenesis/apoptosis also determine skeletal muscle mass during cancer cachexia. Indeed, a decreased skeletal muscle regeneration capacity is observed together with an increased rate of cell death, resulting in muscle wasting. Mitochondrial dysfunction also results in changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators -either released by the tumor or by healthy cells of the cancer patient- are responsible for the activation of these catabolic processes that take place in skeletal muscle.
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain. Electronic address: jargiles@ub.edu.
Josep M
JM
Argilés
D002100:Cachexia / Q000209:etiology; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
Cachexia; Cancer; Inflammation