Skip to main content
Fig. 4 | Inflammation and Regeneration

Fig. 4

From: RANKL biology: bone metabolism, the immune system, and beyond

Fig. 4

RANKL in tumorigenesis and metastasis. a RANKL–RANK interaction in breast cancer. Mutations in BRCA1 lead to the increased expression of RANK in luminal progenitor cells of the mammary gland. The RANKL expressed on PR-expressing LECs (see Fig. 3a) stimulates the proliferation and survival of the mutant cells and DNA repair is impaired in these cells, resulting in the tumorigenesis. b RANKL–RANK interaction in lung cancer. KRAS mutations in the lung epithelial cells increase RANK expression on these cells. These cells undergo excessive proliferation upon RANKL stimulation, leading to tumor development. c RANKL–RANK interaction in multiple myeloma. Myeloma cells enhance RANKL expression on the stromal cells of tumors in the bone, resulting in osteoclastic bone resorption and the release of myeloma cells from dormancy. Together, these processes lead to an expansion of the tumors in the bone. d RANKL–RANK interaction in bone metastasis. Cancer cells metastasized to the bone marrow produce molecules, including PTHrP. Some of these induce RANKL expression on the tumor stromal cells. This RANKL induces osteoclastic bone resorption, and the degraded bone releases growth factors embedded in the matrix, such as IGF-1 and TGF-β. These factors increase the tumor size and the enlarged tumor further contributes to the amount of RANKL expression, forming a vicious cycle. The soluble form of RANKL contributes to the chemotaxis of the tumor cells expressing RANK toward the site of metastasis. Tumoral RANKL is also involved in the angiogenesis and the permeability of the blood vessels, facilitating tumor invasion. RANKL receptor activator of NF-κB ligand, RANK receptor activator of NF-κB, Pg progesterone, PR progesterone receptor, LEC luminal epithelial cell, PTHrP parathyroid hormone-related peptide, IGF insulin-like growth factor, TGF-β transforming growth factor-β

Back to article page