IBMS BoneKEy | Perspective
The many roles of RANKL-RANK signaling in bone, breast and cancer
Daniel Schramek
Josef M Penninger
DOI:10.1138/20110512
Abstract
Receptor activator of nuclear factor-κB ligand (RANKL), its signaling receptor RANK, and its natural decoy receptor OPG are members of the tumor necrosis factor (TNF) and TNF receptor superfamily and are best known for their essential role in controlling osteoclastogenesis. RANKL in bone has also been shown to serve as a chemoattractant for cancer cells, thus explaining the tropism of certain cancers such as breast and prostate cancer to preferentially metastasize to bone. Surprisingly, studies of genetically engineered mice demonstrated that RANKL-RANK signaling is also required for proper formation of a lactating mammary gland and, intriguingly, the development of mammary cancer. RANK-deficient mice show a markedly delayed development of hormone- and oncogen-driven tumorigenesis and RANKL-RANK signaling is required for the proliferation and survival of cancerous mammary epithelial cells. Here we review the physiological functions of RANKL-RANK and how this system might be a key to understanding breast cancer.
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