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

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.