ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells

被引:139
作者
Drake, Justin M. [1 ]
Strohbehn, Garth [1 ]
Bair, Thomas B. [4 ]
Moreland, Jessica G. [3 ]
Henry, Michael D. [1 ,2 ]
机构
[1] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA
[2] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA
[3] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[4] Univ Iowa, DNA Facil, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
关键词
TRANSCRIPTION FACTOR SNAIL; TUMOR-CELLS; E-CADHERIN; MESENCHYMAL TRANSITION; MIR-200; FAMILY; MELANOMA-CELLS; IN-VITRO; METASTASIS FORMATION; PROMOTES METASTASIS; EXPRESSION;
D O I
10.1091/mbc.E08-10-1076
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2207 / 2217
页数:11
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