Document Detail


ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells.
MedLine Citation:
PMID:  19225155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. Instead, TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and up-regulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.
Authors:
Justin M Drake; Garth Strohbehn; Thomas B Bair; Jessica G Moreland; Michael D Henry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-18
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-15     Completed Date:  2009-05-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2207-17     Citation Subset:  IM    
Affiliation:
Department of Molecular Physiology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / metabolism
Cell Line, Tumor
Cell Movement*
Endothelial Cells / metabolism,  pathology*
Epithelial Cells / metabolism,  pathology*
Epithelium / pathology
Gene Expression Regulation, Neoplastic
Homeodomain Proteins / genetics,  metabolism*
Humans
Male
Mesoderm / pathology
Mice
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Phenotype
Prostatic Neoplasms / genetics,  metabolism*,  pathology*
Transcription Factors / genetics,  metabolism*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Cadherins; 0/Homeodomain Proteins; 0/Transcription Factors; 0/ZEB1 protein, human
Comments/Corrections

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