Vannier, C., Mock, K., Brabletz, T., and Driever, W. (2013) Zeb1 regulates E-cadherin and Epcam expression to control cell behavior in early zebrafish development. The Journal of biological chemistry. 288(26):18643-59.
The ZEB1 transcription factor is best-known as inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting
through transcriptional repression of CDH1 (encoding E-cadherin) and the EMT-suppressing miR-200s. Here we analyze roles of
the ZEB1 zebrafish orthologs, Zeb1a and Zeb1b, and of miR-200s in 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 the deep cells of the blastoderm and may
contribute to control of epithelial integrity of enveloping layer cells, the outermost cells of the blastoderm. 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.