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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2015
Journal
Cancer Cell
Volume
27
Issue
2
Pages
193-210
Date Published
2015 Feb 09
ISSN
1878-3686
URL
DOI
10.1016/j.ccell.2014.11.017
PubMed ID
25600338
PubMed Central ID
PMC4326554
Links
Grant list
CA151293 / CA / NCI NIH HHS / United States
K99 CA151293 / CA / NCI NIH HHS / United States
R01 CA148761 / CA / NCI NIH HHS / United States
CA149196-04 / CA / NCI NIH HHS / United States
U54CA149196 / CA / NCI NIH HHS / United States
R01 CA183878 / CA / NCI NIH HHS / United States
U54 CA149196 / CA / NCI NIH HHS / United States
CA148761 / CA / NCI NIH HHS / United States
CA183878 / CA / NCI NIH HHS / United States
R00 CA151293 / CA / NCI NIH HHS / United States