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Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

Oncogene volume 27, pages 4690–4701 (2008)Cite this article

Abstract

Snai1 (Snail) and Snai2 (Slug), the two main members of Snail family factors, are important mediators of epithelial-mesenchymal transitions and involved in tumor progression. We recently reported that Snai1 plays a major role in tumor growth, invasion and metastasis, but the contribution of Snai2 to tumorigenesis is not yet well understood. To approach this question we have silenced Snai2 and/or Snai1 by stable RNA interference in two independent mouse skin carcinoma (HaCa4 and CarB) cell lines. We demonstrate that Snai2 knockdown has a milder effect, but collaborates with Snai1 silencing in reduction of tumor growth potential of either carcinoma cell line when injected into nude mice. Importantly, Snai1 or Snai2 silencing dramatically influences the metastatic ability of squamous carcinoma HaCa4 cells, inducing a strong reduction in liver and lung distant metastasis. However, only Snai1 knockdown has an effective action on invasiveness and fully abolishes tumor cell dissemination into the spleen. These results demonstrate that Snai1 and Snai2 collaborate on primary tumor growth and specifically contribute to site-specific metastasis of HaCa4 cells. These data also indicate that Snai1 is the major regulator of local invasion, supporting a hierarchical participation of both factors in the metastatic process.

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Abbreviations

d.p.i.:

days post-injection

EMT:

epithelial-mesenchymal transition

MDCK:

Madin Darby canine kidney

MMP:

metalloproteinase

MRI:

magnetic resonance imaging

qRT-PCR:

quantitative real-time PCR

RT–PCR:

reverse transcription–PCR

shRNA:

small hairpin interfering RNA

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Acknowledgements

We thank Vanesa Santos for excellent technical assistance, P López for MRI analysis, H Clevers for the pTER-Zeo vector and H Peinado for critical reading of the article. This work was supported by grants from the Spanish Ministry of Education and Science (SAF2004-00361; SAF2007-63051; NAN2004-09230-C04-02; Consolider-Ingenio CSD00C-2007-26102) and the EU (MRTN-CT-2004-005428).

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Author notes

  1. D Olmeda

    Present address: Current address: Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro, Madrid, Spain.,

Authors and Affiliations

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

    D Olmeda, A Montes, G Moreno-Bueno, F Portillo & A Cano

  2. Departamento de Cirugía y Medicina Animal, Facultad de Veterinaria, UCM, Madrid, Spain

    J M Flores

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  1. D Olmeda
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  2. A Montes
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  5. F Portillo
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  6. 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., Montes, A., Moreno-Bueno, G. et al. Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines. Oncogene 27, 4690–4701 (2008). https://doi.org/10.1038/onc.2008.118

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