Fig. 2

Muscle anabolic and catabolic signalings involved in muscle growth and wasting. Growth factors and nutrients activate PI3K-AKT-mTOR pathway, resulting in an increase in muscle protein synthesis. Furthermore, MAPK and SMAD 1/5/8 activation also induces protein transcription, leading to muscle growth. Conversely, in cachexia conditions, inflammatory cytokines from tumors and immune cells induce activation of transcription factor NF-kB, leading to UPS and ALS activation, which leads to muscle wasting. Furthermore, activin and myostatin bind to the ActRIIB, which phosphorylates SMAD2/3, activating UPS. Glucocorticoid and AngII also activate UPS and ALS pathway, respectively, and lead to muscle wasting. GH, growth hormone; IGF1R, IGF1 receptor; IR, Insulin receptor; BMP, bone morphogenetic protein; BMPRII, BMP receptor II; AR, androgen receptor; ActRIIb, activin type II receptor; AngII, Angiotensin II; AT1R, type 1 angiotensin II receptors; IL-6R, Interleukin 6 receptor; IL1bR, IL1b receptor; TNFaR, TNF receptor; PIF, proteolysis-inducing factor; PIFR, proteolysis-inducing factor receptor; GR, glucocorticoid receptor; ROS, Reactive oxygen species; UPS, ubiquitin (Ub)-proteasome system; and ALS, autophagy-lysosome system. The dashed lines indicate inhibited pathways