Snail silencing effectively suppresses tumour growth and invasiveness.
The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour progression. In this report, we provide evidence for this hypothesis. We show that silencing of Snail by stable RNA interference in MDCK-Snail cells induces a complete mesenchymal to epithelial transition (MET), associated to the upregulation of E-cadherin, downregulation of mesenchymal markers and inhibition of invasion. More importantly, stable interference of endogenous Snail in two independent carcinoma cell lines leads to a dramatic reduction of in vivo tumour growth, accompanied by increased tumour differentiation and a significant decrease in the expression of MMP-9 and angiogenic markers and invasiveness. These results indicate that use of RNA interference can be an effective tool for blocking Snail function, opening the way for its application in new antiinvasive therapies.
Olmeda
D
D
Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, c/Arturo Duperier, Madrid, Spain.
Jordá
M
M
Peinado
H
H
Fabra
A
A
Cano
A
A
D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers; D004285:Dogs; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D051379:Mice; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
D015820:Cadherins; D017931:DNA Primers; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors