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

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          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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          Author and article information

          Journal
          Cancer Cell
          Cancer cell
          1878-3686
          1535-6108
          Feb 9 2015
          : 27
          : 2
          Affiliations
          [1 ] Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [2 ] Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [3 ] Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [4 ] NCI Center for Modeling Cancer Development, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA.
          [5 ] NCI Center for Modeling Cancer Development, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA; Department of Radiology, Southeast University School of Medicine, Nanjing 210018, China.
          [6 ] Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China.
          [7 ] Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [8 ] Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [9 ] Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; NCI Center for Modeling Cancer Development, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6670 Bertner Avenue, Houston, TX 77030, USA; Department of Radiology, Houston Methodist Hospital, 6565 Fannin Street, Houston, TX 77459, USA.
          [10 ] Cancer Program, the Eli and Edythe L. Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
          [11 ] Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [12 ] Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
          [13 ] Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; McNair Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: xiangz@bcm.edu.
          Article
          S1535-6108(14)00468-1 NIHMS644614
          10.1016/j.ccell.2014.11.017
          25600338
          a9543825-294f-496b-98d3-67b973fbe309
          Copyright © 2015 Elsevier Inc. All rights reserved.
          History

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