The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

Hai Wang, Cuijuan Yu, Xia Gao, Thomas Welte, Aaron M. Muscarella, Lin Tian, Hong Zhao, Zhen Zhao, Shiyu Du, Jianning Tao, Brendan Lee, Thomas F. Westbrook, Stephen T.C. Wong, Xin Jin, Jeffrey M. Rosen, C. Kent Osborne, Xiang H.F. Zhang

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)193-210
Number of pages18
JournalCancer Cell
Volume27
Issue number2
DOIs
StatePublished - Feb 9 2015

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Wang, H., Yu, C., Gao, X., Welte, T., Muscarella, A. M., Tian, L., Zhao, H., Zhao, Z., Du, S., Tao, J., Lee, B., Westbrook, T. F., Wong, S. T. C., Jin, X., Rosen, J. M., Osborne, C. K., & Zhang, X. H. F. (2015). The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells. Cancer Cell, 27(2), 193-210. https://doi.org/10.1016/j.ccell.2014.11.017