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PMID: 23667256 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Zeb1 regulates E-cadherin and Epcam (epithelial cell adhesion molecule) expression to control cell behavior in early zebrafish development.

The Journal of biological chemistry ·Vol. 288 ·No. 26 ·2013-06-28 ·Pages 18643-59

Vannier C, Mock K, Brabletz T, Driever W

Abstract

The ZEB1 transcription factor is best known as an inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting through transcriptional repression of CDH1 (encoding E-cadherin) and the EMT-suppressing microRNA-200s (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. Furthermore, Zeb1 acts as a 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.

Keywords
Cell Adhesion Development E-cadherin EMT Gastrulation Transcription/Developmental Factors
MeSH Terms
Animals Cadherins/metabolism Cell Adhesion Cell Line, Tumor Cell Nucleus/metabolism Epithelial-Mesenchymal Transition Gastrulation Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Homeodomain Proteins/metabolism,physiology Humans In Situ Hybridization Membrane Glycoproteins/metabolism MicroRNAs/metabolism Microscopy, Confocal/methods Neoplasm Invasiveness Promoter Regions, Genetic Time Factors Transcription Factors/metabolism,physiology Zebrafish/embryology Zebrafish Proteins/metabolism,physiology Zinc Finger E-box-Binding Homeobox 1
Chemicals
Cadherins Cdh1 protein, zebrafish EpCAM protein, zebrafish Homeodomain Proteins Membrane Glycoproteins MicroRNAs Transcription Factors ZEB1 protein, human Zebrafish Proteins Zinc Finger E-box-Binding Homeobox 1 zeb1b protein, zebrafish
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vannier Corinne
Developmental Biology, Institute Biology I, Faculty of Biology, Albert-Ludwigs-University Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
Mock Kerstin
Brabletz Thomas
Driever Wolfgang
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M113.467787
Published
2013-06-28
Epub
2013-00-10
Pages
18643-59
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3696638
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M113.467787 PMC Full Text View journal details
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