The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression

TY - JOUR

T1 - The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression

AU - Cano, A

AU - Pérez-Moreno, M A

AU - Rodrigo, I

AU - Locascio, A

AU - Blanco, M J

AU - del Barrio, M G

AU - Portillo, F

AU - Nieto, M A

PY - 2000/2

Y1 - 2000/2

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Cadherins

KW - Carcinoma

KW - Carcinoma, Squamous Cell

KW - Cell Differentiation

KW - Cell Movement

KW - Cytoskeletal Proteins

KW - DNA-Binding Proteins

KW - Desmoplakins

KW - Epithelial Cells

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Keratinocytes

KW - Mesoderm

KW - Mice

KW - Neoplasm Invasiveness

KW - Neoplasms, Glandular and Epithelial

KW - Phenotype

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - Repressor Proteins

KW - Snail Family Transcription Factors

KW - Transcription Factors

KW - Tumor Cells, Cultured

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/35000025

DO - 10.1038/35000025

M3 - Journal article

C2 - 10655586

SN - 1465-7392

VL - 2

SP - 76

EP - 83

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 2

ER -