Mechanisms to explain wasting of muscle and fat in cancer cachexia.
OBJECTIVE
To describe the most relevant recent findings concerning the molecular mechanisms involved in both fat and muscle tissues in cachectic cancer patients.


RESULTS
Relevant progress has been made in the mechanism of signalling protein metabolism in skeletal muscle. PI3K has a dual role inhibiting protein degradation by inhibition of Atrogin-1 and MuRF1 gene expression and facilitating AKT phosphorylation, leading to increased protein synthesis. Interestingly, Caspase-3 activity is intimately associated with myofibrillar protein degradation in muscle tissue. With respect to fat metabolism, increased lipolysis in human cancer cachexia seems to be directly connected to increased hormone-sensitive lipase activity.


CONCLUSIONS
The results and findings described in this review represent important progress in wasting disease mechanisms and may provide hints for future therapeutic approaches in cancer cachexia.
Argilés
Josep M
JM
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain. jargiles@ub.edu
López-Soriano
Francisco J
FJ
Busquets
Sílvia
S
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D002100:Cachexia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019282:Wasting Syndrome / Q000378:metabolism* / Q000473:pathology; D015431:Weight Loss