Opposite effects of tumor-derived cytokines and mechanical stimulation on muscle stem cell activity and muscle homeostasis

Cancer cachexia is a muscle wasting syndrome, characterized by muscle fiber atrophy and hampered satellite cell (SC) myogenic potential, ultimately leading to morbidity, lowered quality of life, and death. Exercise training improves quality of life and survival of cancer patients and its beneficial effects can be mimicked by wheel running in mice.1,2 In an animal model of cancer cachexia we demonstrated that wheel running counteracts cachexia by releasing the autophagic flux and by lowering Pax7 expression, which blocks SC myogenic progression.3,4. Exercise pleiotropic effects include the alteration of circulating factors in favor of an anti-inflammatory environment and the activation of mechanotransduction pathways in muscle cells. Serum response factor (SRF) is a transcription factor of pivotal importance for muscle homeostasis, which is activated with its co-factor MRTF by mechanotransduction in a way dependent on actin polymerization.5 Our goal was to assess whether mechanotransduction per se is sufficient to elicit exercise effects in the presence of pro-cachectic factors of tumor origin and to characterize the mechanotransduction signals involved.