Document Detail


An in vivo model of epithelial to mesenchymal transition reveals a mitogenic switch.
MedLine Citation:
PMID:  22906417     Owner:  NLM     Status:  MEDLINE    
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 C Jahn; Mary E Law; Patrick E Corsino; Nicole N Parker; Kien Pham; Bradley J Davis; Jianrong Lu; Brian K Law
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-17
Journal Detail:
Title:  Cancer letters     Volume:  326     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2012-12-10     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  183-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Epithelial-Mesenchymal Transition*
Humans
Mice
Mitogens / pharmacology*
Models, Biological
Oligonucleotide Array Sequence Analysis
Grant Support
ID/Acronym/Agency:
R01 CA093651/CA/NCI NIH HHS; R01-CA93651/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Mitogens
Comments/Corrections

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