Current Evidence of the Role of the Myokine Irisin in Cancer

Abstract

Cancer is a disease associated with extreme human suffering, a huge economic cost to health systems, and is the second leading cause of death worldwide. Regular physical activity is associated with many health benefits, including reduced cancer risk. In the past two decades, exercising/contracting skeletal muscles have been found to secrete a wide range of biologically active proteins, named myokines. Myokines are delivered, via the circulation, to different cells/tissues, bind to their specific receptors and initiate signaling cascades mediating the health benefits of exercise. The present review summarizes the existing evidence of the role of the myokine irisin in cancer. In vitro studies have shown that the treatment of various cancer cells with irisin resulted in the inhibition of cell proliferation, survival, migration/ invasion and induced apoptosis by affecting key proliferative and antiapoptotic signaling pathways. However, the effects of irisin in humans remains unclear. Although the majority of the existing studies have found reduced serum irisin levels in cancer patients, a few studies have shown the opposite. Similarly, the majority of studies have found increased levels of irisin in cancer tissues, with a few studies showing the opposite trend. Clearly, further investigations are required to determine the exact role of irisin in cancer.

Keywords: cancer; contraction; exercise; health benefits; in vitro; in vivo; irisin; muscle; myokines.

Figure 1

Myokines mediate the health benefits of exercise. Muscle contractions induce the production and release of myokines by muscle, which are delivered through the blood circulation to different tissues in the body, improving the overall tissue function and providing health benefits. This figure was created with BioRender.com.

Figure 2

Schematic representation of FNDC5 and the irisin protein domains (A). The synthesis and release of irisin by muscle cells is induced by exercise (B). Figure 2B was created with BioRender.com.

Figure 3

Effects of irisin on cancer cell signaling molecules. PI3K, Akt, Bcl-2, NF-κB, STAT3 and mTOR were all inhibited by irisin. Irisin activated AMPK and MAPK. This figure is based on the data of the studies mentioned in the in vitro section and Table 1. The figure was created with BioRender.com.