@article{27873af02c244996b1664a98916eb203,
title = "The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells",
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.",
author = "Hai Wang and Cuijuan Yu and Xia Gao and Thomas Welte and Muscarella, {Aaron M.} and Lin Tian and Hong Zhao and Zhen Zhao and Shiyu Du and Jianning Tao and Brendan Lee and Westbrook, {Thomas F.} and Wong, {Stephen T.C.} and Xin Jin and Rosen, {Jeffrey M.} and Osborne, {C. Kent} and Zhang, {Xiang H.F.}",
note = "Funding Information: We thank Dr. Max Wicha and S. Liu for generously providing us with the immortalized human MSC cells; Dr. Robin L. Anderson for 4T1.2 cells; Baylor Breast Center Pathology Core for technical assistance; and D. Weiss, I.S. Kim, H.C. Lo, and Z. Duan for helpful discussions. X. H.-F. Z. is supported by NCI CA151293, CA183878, Breast Cancer Research Foundation, U.S. Department of Defense DAMD W81XWH-13-1-0195, a Pilot Award of CA149196-04, and McNair Medical Institute. H.W. is supported by U.S. Department of Defense DAMD W81XWH-13-1-0296. H. Z. and S.T.C.W. are supported by NIH grant U54CA149196, John S. Dunn Research Foundation, and Ting Tsung and Wei Fong Chao Foundation. Studies with the p53 null tumors were supported by NIH grant CA148761 to J.M.R. C.K.O. is a member on the advisory boards for Genentech, Novartis, Nanostring, AstraZeneca, and Pfizer. ",
year = "2015",
month = feb,
day = "9",
doi = "10.1016/j.ccell.2014.11.017",
language = "English (US)",
volume = "27",
pages = "193--210",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}