The Transcription Factor Snail Controls Epithelial-Mesenchymal Transitions by Repressing E-cadherin Expression

Nat Cell Biol. 2000 Feb;2(2):76-83. doi: 10.1038/35000025.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Carcinoma / pathology
  • Carcinoma, Squamous Cell / pathology
  • Cell Differentiation
  • Cell Movement
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Desmoplakins
  • Epithelial Cells / cytology*
  • Gene Expression Regulation, Developmental*
  • Humans
  • Keratinocytes / cytology
  • Mesoderm / cytology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasms, Glandular and Epithelial / pathology
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Binding
  • Repressor Proteins / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Desmoplakins
  • Repressor Proteins
  • Snail Family Transcription Factors
  • Transcription Factors