Mechanism of muscle wasting in cancer cachexia
Loss of body weight from muscle wasting is the leading cause of death in cancer cachexia and dietary intervention is the primary therapeutics to prevent muscle wasting.
Cancer cells consume serine and is necessary to preserve skeletal muscle structure and functionality.
The researchers demonstrate that decreased serine availability during tumor progression promotes myotubes diameter reduction in vitro and induces muscle wasting in in vivo mice models.
Authors also found that myofibers incubated with tumor media or serine-free media showed reduced diameter, inhibits AKTmTORC1 pathway, protein synthesis, increased protein degradation, and enhanced expression of the muscle atrophy-related genes Atrogin1 and MuRF1. In addition, they also found oxidative stress in myotubes in the absence of serine.
Consistently, serine dietary deprivation strongly strengthens cancer-associated weight loss and muscle atrophy in mice models.
Theus, serine consumption by tumor cells is the primary driver in cancer cachexia.
