Open AccessZ inc finger E ‐box binding homeobox 1 promotes vasculogenic mimicry in colorectal cancer through induction of epithelial‐to‐mesenchymal transition
Author(s) -
Liu Zhiyong,
Qi Lisha,
Li Hui,
Gao Jun,
Leng Xue
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02199.x
Subject(s) - vasculogenic mimicry , epithelial–mesenchymal transition , gene knockdown , homeobox , cancer research , zinc finger , colorectal cancer , cadherin , biology , immunohistochemistry , klf4 , vimentin , microbiology and biotechnology , sox2 , chemistry , cancer , cell culture , transcription factor , immunology , metastasis , cell , gene , genetics
Our previous studies have shown that epithelial–mesenchymal transition ( EMT ) may be involved in the vasculogenic mimicry (VM) formation in hepatocellular carcinoma. Here, we hypothesize that zinc finger E ‐box binding homeobox 1 ( ZEB 1) promotes VM formation in colorectal carcinoma ( CRC ) by inducing EMT . We identified VM in 39 (19.2%) out of 203 CRC patients. The presence of VM was associated with aggressive biological behavior and was an unfavorable prognostic indicator. By immunohistochemical analysis, we found that the VM ‐positive CRC samples showed increased ZEB 1 expression compared with the VM ‐negative samples and the ZEB 1 expression occurred concomitantly with features of EMT . In vitro , knockdown of ZEB 1 in poorly differentiated HCT 116 CRC cells destroyed the vessel‐like structures in the 3‐ D culture, a property associated with VM formation. Knockdown of ZEB 1 resulted in restoration of epithelial phenotypes and significantly inhibited the ability to migrate and invade. In addition, ZEB 1 underexpression decreased the expression of vascular endothelial ( VE )‐cadherin and F lk‐1, which are characteristics of endothelial cells. Taken together, our results suggest that ZEB 1 can promote VM formation by inducing EMT in CRC and might represent an important target in CRC . ( Cancer Sci 2012; 103: 813–820)