1. Snail Induction of Epithelial to Mesenchymal Transition in Tumor Cells Is Accompanied by MUC1 Repression andZEB1 Expression
- Author
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Josep Baulida, Eduard Batlle, David Domı́nguez, Elena Sancho, Marta Garrido, Clara Francí, Isabel Puig, Antonio García de Herreros, Shoukat Dedhar, and Sandra Guaita
- Subjects
DNA, Complementary ,Transcription, Genetic ,Blotting, Western ,Down-Regulation ,Snail ,Transfection ,Biochemistry ,Cell Line ,Mesoderm ,Mice ,Dogs ,Transcription (biology) ,biology.animal ,parasitic diseases ,Tumor Cells, Cultured ,Animals ,Humans ,Epithelial–mesenchymal transition ,Cloning, Molecular ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,MUC1 ,Cell Nucleus ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Mucin-1 ,fungi ,Epithelial Cells ,Promoter ,DNA ,Cell Biology ,Fibroblasts ,Tetracycline ,Blotting, Northern ,Molecular biology ,Up-Regulation ,DNA-Binding Proteins ,Repressor Proteins ,Microscopy, Electron ,Phenotype ,Cell culture ,Keratins ,RNA ,Snail Family Transcription Factors ,Protein Binding ,Transcription Factors - Abstract
E-cadherin protein plays a key role in the establishment and maintenance of adherent junctions. Recent evidence implicates the transcription factor Snail in the blockage of E-cadherin expression in fibroblasts and some epithelial tumor cells through direct binding to three E-boxes in the E-cadherin promoter. Transfection of Snail into epithelial cells leads to a more fibroblastic phenotype. Cells expressing Snail presented a scattered flattened phenotype with low intercellular contacts. Other epithelial markers like Cytokeratin 18 or MUC1 were also repressed. The effects of Snail on MUC1 transcription were mediated by two E-boxes present in the proximal promoter. Snail also induced expression of the mesenchymal markers fibronectin and LEF1 and the transcription repressor ZEB1. ZEB1 and Snail had a similar pattern of expression in epithelial cell lines, and both were induced by overexpression of ILK1, a kinase that causes the loss of E-cadherin and the acquisition of a fibroblastic phenotype. Snail overexpression in several cell lines raised ZEB1 RNA levels and increased the activity of ZEB1 promoter. ZEB1 could also repress E-cadherin and MUC1 promoters but less strongly than Snail. However, since ZEB1 expression persisted after Snail was down-regulated, ZEB1 may regulate epithelial genes in several tumor cell lines.
- Published
- 2002
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