Research Paper Volume 4, Issue 2 pp 133—143
Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting
Figure 6. A proposed model of IL-6 dependent loss of sarcomeric integrity a nd function involving MEF2C.
Expression and activity of MEF2C are regulated by calcineurin. Chronic activation of IL-6 signaling in skeletal muscle results in an upregulated expression of SOCS3. SOCS3 has been shown to delocalize calcineurin from its usual Z-line position to the periphery of a myofiber. This might affect its function and hence impact on the downstream targets like MEF2C. Since MEF2C is a key regulator of many myogenic and energy homeostatic molecules, any perturbation in its activity could greatly affect muscle performance and integrity. Such alterations may accelerate muscle breakdown and disintegration of the tissue contributing to fatigue and weakness during cancer cachexia.