The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells

Cancer Cell. 2015 Feb 9;27(2):193-210. doi: 10.1016/j.ccell.2014.11.017. Epub 2015 Jan 15.


Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cell Line, Tumor
  • Female
  • Humans
  • Neoplasm Staging
  • Osteogenesis / genetics*
  • TOR Serine-Threonine Kinases / genetics
  • Tumor Microenvironment / genetics*


  • Cadherins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases