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
  • View Affiliations

  • Published online on: April 1, 2003     https://doi.org/10.3892/ijo.22.4.891
  • Pages: 891-898
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

April 2003
Volume 22 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yokoyama K, Kamata N, Fujimoto R, Tsutsumi S, Tomonari M, Taki M, Hosokawa H and Nagayama M: Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. Int J Oncol 22: 891-898, 2003
APA
Yokoyama, K., Kamata, N., Fujimoto, R., Tsutsumi, S., Tomonari, M., Taki, M. ... Nagayama, M. (2003). Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas. International Journal of Oncology, 22, 891-898. https://doi.org/10.3892/ijo.22.4.891
MLA
Yokoyama, K., Kamata, N., Fujimoto, R., Tsutsumi, S., Tomonari, M., Taki, M., Hosokawa, H., Nagayama, M."Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas". International Journal of Oncology 22.4 (2003): 891-898.
Chicago
Yokoyama, K., Kamata, N., Fujimoto, R., Tsutsumi, S., Tomonari, M., Taki, M., Hosokawa, H., Nagayama, M."Increased invasion and matrix metalloproteinase-2 expression by Snail-induced mesenchymal transition in squamous cell carcinomas". International Journal of Oncology 22, no. 4 (2003): 891-898. https://doi.org/10.3892/ijo.22.4.891