Snail silencing effectively suppresses tumour growth and invasiveness
Open Access
- 9 October 2006
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 26 (13) , 1862-1874
- https://doi.org/10.1038/sj.onc.1209997
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- Repression of Na,K-ATPase β1-Subunit by the Transcription Factor Snail in CarcinomaMolecular Biology of the Cell, 2004
- The transcription factor Slug repressesE-cadherinexpression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressorsJournal of Cell Science, 2003
- Correlation of Snail expression with histological grade and lymph node status in breast carcinomasOncogene, 2002
- Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systemsProceedings of the National Academy of Sciences, 2001
- The Two-Handed E Box Binding Zinc Finger Protein SIP1 Downregulates E-Cadherin and Induces InvasionMolecular Cell, 2001
- Evidence for a function of CtBP in epithelial gene regulation and anoikisOncogene, 2000
- The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expressionNature Cell Biology, 2000
- The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cellsNature Cell Biology, 2000
- The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor geneTrends in Biochemical Sciences, 1999
- Cell adhesion in invasion and metastasisSeminars in Cell Biology, 1992