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Title:
Snail silencing effectively suppresses tumour growth and invasiveness | Oncogene
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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.
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nature portfolio permissions reprints privacy policy advertising cell-adhesion molecule e-cadherin nature 392 nature zinc-finger transcription factors small double-stranded rnas social media mdck-snail cells induces pb01 suppresses radio-resistance k-atpase beta1-subunit repressing e-cadherin expression regulating atr signaling e-cadherin gene expression springerlink instant access personal data invasive phenotype linked author correspondence epithelial tumour cells data protection permissions egf-induced emt transcription factor snail snail transcription factor cancer gene therapy cell death vivo tumour growth metalloproteinase rt–pcr transcriptional repressor snail e-cadherin expression perez-moreno ma transcription factors slug vitro cell technologies transcription factors snail privacy tumour cell interactions block tumour progression e-cadherin downregulation cancer cell 8 supplementary figure s2 supplementary figure s3 supplementary figure s4 supplementary figure s5 supplementary figure s6 issue learn epithelial–mesenchymal transitions tumour cells breast carcinomas
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headline:Snail silencing effectively suppresses tumour growth and invasiveness
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description: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 epithelialâmesenchymal 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.
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