• Open Access

Zinc finger E-box binding homeobox 1 promotes vasculogenic mimicry in colorectal cancer through induction of epithelial-to-mesenchymal transition

Authors

  • Zhiyong Liu,

    1. Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin
    2. The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin
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    • Zhiyong Liu and Baocun Sun contributed equally to this study.
  • Baocun Sun,

    Corresponding author
    1. The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin
    2. Department of Pathology, Tianjin Medical University, Tianjin, China
    • Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin
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    • Zhiyong Liu and Baocun Sun contributed equally to this study.
  • Lisha Qi,

    1. Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin
    2. The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin
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  • Hui Li,

    1. Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin
    2. The Key Laboratory of Tianjin Cancer Prevention and Treatment, Tianjin
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  • Jun Gao,

    1. Department of Pathology, Tianjin Medical University, Tianjin, China
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  • Xue Leng

    1. Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin
    2. Department of Pathology, Tianjin Medical University, Tianjin, China
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To whom all correspondence should be addressed.

E-mail: baocunsun@gmail.com

Abstract

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 (ZEB1) 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 ZEB1 expression compared with the VM-negative samples and the ZEB1 expression occurred concomitantly with features of EMT. In vitro, knockdown of ZEB1 in poorly differentiated HCT116 CRC cells destroyed the vessel-like structures in the 3-D culture, a property associated with VM formation. Knockdown of ZEB1 resulted in restoration of epithelial phenotypes and significantly inhibited the ability to migrate and invade. In addition, ZEB1 underexpression decreased the expression of vascular endothelial (VE)-cadherin and Flk-1, which are characteristics of endothelial cells. Taken together, our results suggest that ZEB1 can promote VM formation by inducing EMT in CRC and might represent an important target in CRC. (Cancer Sci 2012; 103: 813–820)

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