The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites Journal Article

   

Authors:	Gao, H.; Chakraborty, G.; Lee-Lim, A. P.; Mo, Q.; Decker, M.; Vonica, A.; Shen, R.; Brogi, E.; Brivanlou, A. H.; Giancotti, F. G.
Article Title:	The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites
Abstract:	The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands. Whereas Coco enhances the manifestation of traits associated with cancer stem cells, BMP signaling suppresses it. Coco induces a discrete gene expression signature, which is strongly associated with metastatic relapse to the lung, but not to the bone or brain in patients. Experiments in mouse models suggest that these latter organs contain niches devoid of bioactive BMP. These findings reveal that metastasis-initiating cells need to overcome organ-specific antimetastatic signals in order to undergo reactivation. © 2012 Elsevier Inc.
Keywords:	controlled study; unclassified drug; nonhuman; mouse; metastasis; breast cancer; gene expression; bone morphogenetic protein; transforming growth factor beta; animal experiment; animal model; transcription factor; lung metastasis; cancer cell; cancer stem cell; dormancy; cytokine receptor antagonist; gain of function mutation; coco
Journal Title:	Cell
Volume:	150
Issue:	4
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2012-08-17
Start Page:	764
End Page:	779
Language:	English
DOI:	10.1016/j.cell.2012.06.035
PROVIDER:	scopus
PUBMED:	22901808
PMCID:	PMC3711709
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84865218588&partnerID=40&md5=9c91f26e1348812af1e30b13a7288ba1
Notes:	--- - "Export Date: 1 October 2012" - "CODEN: CELLB" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/33737