The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes

• Published in: Oncogene Vol. 27; no. 27; pp. 3875 - 3879
• Main Authors: Whiteman, E L, Liu, C-J, Fearon, E R, Margolis, B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.06.2008; Nature Publishing; Nature Publishing Group
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cell adhesion & migration; Cell Biology; Cell junctions; Cell Line; Cell Membrane - physiology; Cell Movement - physiology; Cell physiology; Cell Polarity - genetics; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA binding proteins; Dogs; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - physiology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Gene silencing; Genetics; Human Genetics; Internal Medicine; Kidney; Localization; Medicine; Medicine & Public Health; Membrane Glycoproteins - genetics; Membrane proteins; Mesenchyme; Mesoderm - cytology; Mesoderm - physiology; Molecular and cellular biology; Oncology; Physiological aspects; Polarity; Proteins; short-communication; Snail Family Transcription Factors; Snail protein; Snails; Tight Junctions - genetics; Tight Junctions - physiology; Transcription Factors - metabolism; Transforming growth factor-b; United States; Crumbs; epithelial to mesenchymal transition; Snail; apico-basal polarity; tight junction; Mesenchyma; Gastropoda; Repression; Epithelium; Gene expression; Carcinogenesis; Invertebrata; Mollusca; Transcription factor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2008.9

In epithelial cells, the tight junction divides the plasma membrane into distinct apical and basolateral domains. Polarization is essential for epithelial cell function, and apico-basal cell polarity is lost during the epithelial to mesenchymal transition (EMT), a program of events characterized not only by loss of cell polarity, but also by enhanced cell motility and increased cell invasion. Among several apically localized protein complexes, the Crumbs and Par protein complexes have pivotal roles in control of epithelial polarity and apical membrane formation. Here, we demonstrate that the Snail transcriptional repressor antagonizes expression of the Crumbs polarity complex. We show that Snail abolishes localization of the Crumbs and Par complexes to the tight junction, decreases Crumbs complex protein levels and suppresses Crumbs3 transcription. Evidence that Snail acts directly to antagonize Crumbs3 promoter activity is presented. Strikingly, we note that reexpression of exogenous Crumbs3 in Snail-expressing Madin–Darby Canine Kidney cells partially restores cell–cell junctions. Moreover, we find that the EMT inducer transforming growth factor-β elicits transcriptional repression of Crumbs3 and results in a measurable loss of Crumbs3 protein. Our findings provide new insights into the links between the transcriptional repression function of Snail and its role in antagonizing key apico-basal polarity factors during EMT.