Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

Abstract

Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia.

Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer

“…Resistance exercise has traditionally been proposed to fight cachexia and other forms of muscle atrophy because it is a type of exercise that increases muscle protein content balance, mass, strength and resistance to fatigue. Here, we show that wheel running, which shares the features of endurance training 44 , effectively counteracts muscle wasting; as opposed to activating pro-hypertrophic signaling pathways 14 , this type of exercise counteracts pro-atrophic NF-κB-dependent signaling 45 . We observed a significant increase in life span in wheel running C26-bearing mice.…”

Methodological validation of a vertical ladder with low intensity shock stimulus for resistance training in C57BL/6 mice: Effects on muscle mass and strength, body composition, and lactate plasma levels

“…The SPA group condition was performed in a closed enriched environment (plastic box) with 60 cm in length, 30 cm in width and 45 cm in height ( Figure S2). This environment was composed of seesaw, wheel, balls, and tunnels (Coletti et al, 2016;Hutchinson, Avery, & VandeWoude, 2005;Van de Weerd et al, 2002). The condition of the RE group was performed using a vertical ladder 110 cm high with an inclination of 80 ° inclination ( Figure S1c).…”

Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation

“…Worth noting, chemotherapy, used against cancer, induces cachexia and muscle wasting per se [17]. We and others have shown that cachexia is characterized by increased inflammatory markers in the skeletal muscle and by satellite cell activation [18,19]. However, in cachexia satellite cells fail to fuse with muscle fibers and their impairment contributes to muscle wasting [20][21][22].…”