期刊
CANCER CELL
卷 27, 期 2, 页码 193-210出版社
CELL PRESS
DOI: 10.1016/j.ccell.2014.11.017
关键词
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资金
- NCI [CA151293, CA183878]
- Breast Cancer Research Foundation
- U.S. Department of Defense DAMD [W81XWH-13-1-0195, CA149196-04, W81XWH-13-1-0296]
- McNair Medical Institute
- NIH [U54CA149196, CA148761]
- John S. Dunn Research Foundation
- Ting Tsung and Wei Fong Chao Foundation
Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironnnent 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.
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