4.5 Article

Zeb1-mediated T-cadherin repression increases the invasive potential of gallbladder cancer

Journal

FEBS LETTERS
Volume 583, Issue 2, Pages 430-436

Publisher

WILEY
DOI: 10.1016/j.febslet.2008.12.042

Keywords

Gallbladder cancer; T-cadherin; Zeb1; Epithelial-mesenchymal transition; Cancer invasion

Funding

  1. Ministry of Education of Japan [12670165, 13670177, 17590270]
  2. The Kochi University President's Discretionary Grant
  3. Grants-in-Aid for Scientific Research [17590270, 13670177, 12670165] Funding Source: KAKEN

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Here, we report that the transcriptional regulator Zeb1 repressed the transcription of T-cadherin, to increase the invasive activity of gallbladder cancer cells. Zeb1 physically bound to the promoter of T-cadherin, repressed promoter activity in E-box-like sequence-dependent fashion, and suppressed T-cadherin expression. In gallbladder cancer tissues, Zeb1 was expressed at the cancer invasion front, whereas T-cadherin was exclusively expressed in non-invasive foci. Collagen gel invasion assay showed that T-cadherin was a negative regulator for gallbladder cancer invasion. These findings suggest that Zeb1 represses T-cadherin expression and thus increases the invasive activity of gallbladder cancer. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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