Zeb1 regulates E-cadherin and Epcam expression to control cell behavior in early zebrafish development
10.05.2013
Vannier C, Mock K, Brabletz T, Driever W.
J Biol Chem. 2013 May 10. [Epub ahead of print]
The ZEB1 transcription factor an inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting through repression of E-cadherin and the miR-200s. Here we show that the zebrafish Zeb1 orthologs control of cell adhesion and morphogenesis during gastrulation and segmentation stages. Loss and gain of function analyses revealed that Zeb1 represses cdh1 expression to fine-tune adhesiveness of migrating deep blastodermal cells. Further, Zeb1 acts as repressor of Epcam in deep cellsand may contribute to control of epithelial integrity of enveloping layer cells. We found a similar ZEB1-dependent repression of EPCAM expression in human pancreatic and breast cancer cell lines, mediated through direct binding of ZEB1 to the EPCAM promoter. Thus, Zeb1 proteins employ several evolutionary conserved mechanisms to regulate cell-cell adhesion during development and cancer.
