Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas

  • Authors: Kazuhiro Yokoyama, Nobuyuki Kamata, Ryoichi Fujimoto, Satoshi Tsutsumi, Mayumi Tomonari, Masayuki Taki, Hiroyoshi Hosokawa, Masaru Nagayama
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  • Published online on: Tuesday, April 1, 2003
  • Pages: 891-898
  • DOI: 10.3892/ijo.22.4.891

Abstract

Loss of E-cadherin expression is a major characteristic of highly invasive and metastatic cancers. Epithelial-mesenchymal transition (EMT) has been advocated to be a causative mechanism for the suppression of E-cadherin and tumor progression. Snail is a zinc finger transcription factor that triggers the EMT and is one of the recently identified E-cadherin repressors. The reverse correlation of Snail and E-cadherin expressions has been reported in many types of human cancers including squamous cell carcinoma (SCC). In this study, we showed that three E-cadherin negative SCC cell lines had a fibroblastic morphology, strong expressions of vimentin, a mesenchymal marker gene, and Snail. Compared to other E-cadherin positive SCC cells, these cells showed higher invasive ability and expression of MMP-2, a matrix degrading enzyme which has been demonstrated to be highly expressed in invasive cancer cells. Over-expression of Snail in A431 cells resulted in the loss of E-cadherin expression, the change of their morphology to fibroblastic, and the up-regulation of vimentin gene expression, indicating that an EMT was induced by Snail. Furthermore, these cells became more invasive and showed higher levels of MMP-2 activity and its gene expression. Luciferase analysis demonstrated that the MMP-2 promoter activity was induced by Snail transfection and the promoter region from -262 to -411 relative to the transcriptional start site was necessary for this induction. These results indicate that Snail is a new inducer of MMP-2 expression and suggest that the EMT contributes to the increased invasion not only through the inhibition of cell-cell adhesion but also the up-regulation of MMP-2 expression in SCC cells.
Journal Cover

April 2003
Volume 22 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Yokoyama, K., Kamata, N., Fujimoto, R., Tsutsumi, S., Tomonari, M., Taki, M., Hosokawa, H., & Nagayama, M. (2003). Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. International Journal of Oncology, 22(4), 891-898.
MLA
Yokoyama, Kamata, Fujimoto, Tsutsumi, Tomonari, Taki, Hosokawa, and Masaru Nagayama. "Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas." International Journal of Oncology International Journal of Oncology 22.4 (2003): 891-898.
Chicago
Yokoyama, Kamata, Fujimoto, Tsutsumi, Tomonari, Taki, Hosokawa, and Masaru Nagayama. "Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas." International Journal of Oncology International Journal of Oncology 22 no. 4 (2003): 891-898.