The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression.
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.
Cano
A
A
Instituto de Investigaciones Biomédicas, Arturo Duperier 4, 28029 Madrid, Spain. acano@iib.uam.es
Pérez-Moreno
M A
MA
Rodrigo
I
I
Locascio
A
A
Blanco
M J
MJ
del Barrio
M G
MG
Portillo
F
F
Nieto
M A
MA
D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002277:Carcinoma / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051180:Desmoplakins; D004847:Epithelial Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051180:Desmoplakins; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors