The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer

The RANK-RANKL-OPG system is a complex signaling pathway that plays a critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. RANKL signaling promotes osteoclast differentiation and activation, which leads to bone resorption. OPG is a decoy receptor that binds to RANKL and inhibits its signaling. In cancer cells, RANKL expression is often increased, which can lead to increased bone resorption and the development of bone metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown to be effective in the treatment of skeletal-related events, including osteoporosis or bone metastases, and cancer. This review will provide a comprehensive overview of the functions of the RANK-RANKL-OPG system in bone metabolism, mammary epithelial cells, immune function, and cancer, together with the potential therapeutic implications of the RANK-RANKL pathway for cancer management.

Automated summary

The RANK-RANKL-OPG system is a crucial signaling pathway in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL binds to RANK on osteoclasts, dendritic cells, T cells, and other cells, promoting osteoclast differentiation and activation, resulting in bone resorption. OPG acts as a decoy receptor to inhibit RANKL signaling. Increased RANKL expression in cancer cells can lead to enhanced bone resorption and bone metastases. RANKL-neutralizing antibodies, like denosumab, have shown efficacy in treating skeletal-related events and cancer.