Journal article
ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells
Molecular biology of the cell, Vol.20(8), pp.2207-2217
04/15/2009
DOI: 10.1091/mbc.E08-10-1076
PMCID: PMC2669028
PMID: 19225155
Abstract
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.
Details
- Title: Subtitle
- ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells
- Creators
- Justin M. Drake - University of IowaGarth Strohbehn - University of IowaThomas B. Bair - University of IowaJessica G. Moreland - University of IowaMichael D. Henry - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.20(8), pp.2207-2217
- Publisher
- Amer Soc Cell Biology
- DOI
- 10.1091/mbc.E08-10-1076
- PMID
- 19225155
- PMCID
- PMC2669028
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Number of pages
- 11
- Grant note
- T32GM067795 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 0610074Z; 0750196Z / American Heart Association
- Language
- English
- Date published
- 04/15/2009
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Radiation Oncology
- Record Identifier
- 9984302187602771
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