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.
Adachi
Yoshihiro
Y
Department of Pathology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Takeuchi
Tamotsu
T
Nagayama
Tomoko
T
Ohtsuki
Yuji
Y
Furihata
Mutsuo
M
D015820:Cadherins / Q000235:genetics*; D015536:Down-Regulation; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; C099972:H-cadherin; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1