Abstract
The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.
| Original language | English |
|---|---|
| Journal | Nature Cell Biology |
| Volume | 2 |
| Issue number | 2 |
| Pages (from-to) | 76-83 |
| Number of pages | 8 |
| ISSN | 1465-7392 |
| DOIs | |
| Publication status | Published - Feb 2000 |
Keywords
- Animals
- Binding Sites
- Cadherins
- Carcinoma
- Carcinoma, Squamous Cell
- Cell Differentiation
- Cell Movement
- Cytoskeletal Proteins
- DNA-Binding Proteins
- Desmoplakins
- Epithelial Cells
- Gene Expression Regulation, Developmental
- Humans
- Keratinocytes
- Mesoderm
- Mice
- Neoplasm Invasiveness
- Neoplasms, Glandular and Epithelial
- Phenotype
- Promoter Regions, Genetic
- Protein Binding
- Repressor Proteins
- Snail Family Transcription Factors
- Transcription Factors
- Tumor Cells, Cultured
- Journal Article
- Research Support, Non-U.S. Gov't