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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2015 Jan 21

PMID 25600338

Citations 217

Authors

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

Affiliations

Soon will be listed here.

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.

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