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An In Vivo Model of Epithelial to Mesenchymal Transition Reveals a Mitogenic Switch.
MedLine Citation:
PMID:  22906417     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The Epithelial to Mesenchymal Transition (EMT) is a process by which differentiated epithelial cells transition to a mesenchymal phenotype. EMT enables the escape of epithelial cells from the rigid structural constraints of the tissue architecture to a phenotype more amenable to cell migration and, therefore, invasion and metastasis. We characterized an in vivo model of EMT and discovered that marked changes in mitogenic signaling occurred during this process. DNA microarray analysis revealed that the expression of a number of genes varied significantly between post-EMT and pre-EMT breast cancer cells. Post-EMT cancer cells upregulated mRNA encoding c-Met and the PDGF and LPA receptors, and acquired increased responsiveness to HGF, PDGF, and LPA. This rendered the post-EMT cells responsive to the growth inhibitory effects of HGF, PDGF, and LPA receptor inhibitors/antagonists. Furthermore, post-EMT cells exhibited decreased basal Raf and Erk phosphorylation, and in comparison to pre-EMT cells, their proliferation was poorly inhibited by a MEK inhibitor. These studies suggest that therapies need to be designed to target both pre-EMT and post-EMT cancer cells and that signaling changes in post-EMT cells may allow them to take advantage of paracrine signaling from the stroma in vivo.
Authors:
Stephan Jahn; Mary E Law; Patrick Corsino; Nicole N Parker; Kien Pham; Bradley J Davis; Jianrong Lu; Brian K Law
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-17
Journal Detail:
Title:  Cancer letters     Volume:  -     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ireland Ltd.
Affiliation:
Department of Pharmacology and Therapeutics, University of Florida, P.O. Box 100267 1600 SW Archer Road Academic Research Building, Room R5-210 Gainesville, Florida 32610.
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