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  • Original Article
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Snail silencing effectively suppresses tumour growth and invasiveness

Oncogene volume 26, pages 1862–1874 (2007)Cite this article

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.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

EMT:

epithelial–mesenchymal transition

LOXL2:

lysyl oxidase like-2

MET:

mesenchymal–epithelial transition

MDCK:

Madin Darby canine kidney

shRNA:

small hairpin interfering RNA

MMP:

metalloproteinase

RT–PCR:

reverse transcription-polymerase chain reaction

qRT–PCR:

quantitative real-time PCR

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Acknowledgements

We thank Amalia Montes and Vanesa Santos for excellent technical assistance. This work was supported by grants from the biotech company Advanced in vitro Cell Technologies SL (Advancell) and from the Spanish Ministry of Science and Technology (SAF2004-00361; SAF2005-03259; NAN2004-09230-C04-02) and Instituto de Salud Carlos III (RTICCC, FIS03/C03/10; PI050656).

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Author notes

  1. A Cano: Dedicated to the memory of Senén Vilaró, founder of Advanced In Vitro Cell Technologies, SL.

Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas ‘Alberto Sols’ CSIC-UAM, c/Arturo Duperier, Madrid, Spain

    D Olmeda, H Peinado & A Cano

  2. Institut d'Investigació Bellvitge, IDIBELL, Barcelona, Spain

    M Jordá & Á Fabra

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  1. D Olmeda
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  2. M Jordá
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  5. A Cano
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Correspondence to A Cano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Olmeda, D., Jordá, M., Peinado, H. et al. Snail silencing effectively suppresses tumour growth and invasiveness. Oncogene 26, 1862–1874 (2007). https://doi.org/10.1038/sj.onc.1209997

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