TGF-β-Id1 signaling opposes twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition Journal Article

   

Authors:	Stankic, M.; Pavlovic, S.; Chin, Y.; Brogi, E.; Padua, D.; Norton, L.; Massagué, J.; Benezra, R.
Article Title:	TGF-β-Id1 signaling opposes twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition
Abstract:	ID genes are required for breast cancer colonization of the lungs, but the mechanism remains poorly understood. Here, we show that Id1 expression induces a stem-like phenotype in breast cancer cells while retaining epithelial properties, contrary to the notion that cancer stem-like properties are inextricably linked to the mesenchymal state. During metastatic colonization, Id1 induces a mesenchymal-to-epithelial transition (MET), specifically in cells whose mesenchymal state is dependent on the Id1 target protein Twist1, but not at the primary site, where this state is controlled by the zinc finger protein Snail1. Knockdown of Id expression in metastasizing cells prevents MET and dramatically reduces lung colonization. Furthermore, Id1 is induced by transforming growth factor (TGF)-β only in cells that have first undergone epithelial-to-mesenchymal transition (EMT), demonstrating that EMT is a prerequisite for subsequent Id1-induced MET during lung colonization. Collectively, these studies underscore the importance of Id-mediated phenotypic switching during distinct stages of breast cancer metastasis. © 2013 The Authors.
Journal Title:	Cell Reports
Volume:	5
Issue:	5
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2013-12-12
Start Page:	1228
End Page:	1242
Language:	English
DOI:	10.1016/j.celrep.2013.11.014
PROVIDER:	scopus
PMCID:	PMC3891470
PUBMED:	24332369
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84890192124&partnerID=40&md5=6cb0616192a8ac305efa7b70fb3455f9
Notes:	Export Date: 2 January 2014 -- Source: Scopus

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