RANKL/RANK - from bone physiology to breast cancer

Cytokine Growth Factor Rev. 2014 Apr;25(2):205-14. doi: 10.1016/j.cytogfr.2014.01.002. Epub 2014 Jan 10.


RANK and its ligand RANKL are key molecules in bone metabolism and are critically involved in pathologic bone disorders. Deregulation of the RANK/RANKL system is for example a main reason for the development of postmenopausal osteoporosis, which affects millions of women worldwide. Another essential function of RANK and RANKL is the development of a functional lactating mammary gland during pregnancy. Sex hormones, in particular progesterone, induce RANKL expression resulting in proliferation of mammary epithelial cells. Moreover, RANK and RANKL have been shown to regulate mammary epithelial stem cells. RANK and RANKL were also identified as critical mechanism in the development of hormone-induced breast cancer and metastatic spread to bone. In this review, we will focus on the various RANK/RANKL functions ranging from bone physiology, immune regulation, and initiation of breast cancer.

Keywords: Bone; Breast cancer; Mammary gland; RANK; RANKL.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Bone Diseases / metabolism
  • Bone Neoplasms / pathology
  • Bone and Bones / metabolism
  • Bone and Bones / physiology*
  • Breast Neoplasms / pathology
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Humans
  • Mice
  • NF-kappa B / genetics
  • Osteoporosis
  • Osteoprotegerin / genetics
  • Osteoprotegerin / physiology*
  • RANK Ligand / physiology*
  • Receptor Activator of Nuclear Factor-kappa B / physiology*


  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human