Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

SLUG in cancer development

Oncogene volume 24, pages 3073–3082 (2005)Cite this article

Abstract

The SNAIL-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to contribute to piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. While aberrant induction of SLUG has been documented in cancer cells, relatively little is known about the consequences of SLUG overexpression in malignancy. To investigate the potential role of SLUG overexpression in development and in cancer, we generated mice carrying a tetracycline-repressible Slug transgene. These mice were morphologically normal at birth, and developed mesenchymal tumours (leukaemia and sarcomas) in almost all cases examined. Suppression of the Slug transgene did not rescue the malignant phenotype. Furthermore, the BCR–ABL oncogene, which induces Slug expression in leukaemic cells, did not induce leukaemia in Slug-deficient mice, implicating Slug in BCR–ABL leukaemogenesis in vivo. Overall, the findings indicate that while Slug overexpression is not sufficient to cause overt morphogenetic defects in mice, they demonstrate a specific and critical role for Slug in the pathogenesis of mesenchymal tumours.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Batlle E, Sancho E, FRanci C, Dominguez D, Monfar M, Baulida J and de Herreros AG . (2000). Nat. Cell Biol., 2, 84–89.

  • Becker MW and Clarke MF . (2002). Cancer Cell, 2, 249–251.

  • Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F and Nieto MA . (2000). Nat. Cell Biol., 2, 76–83.

  • Clark SS, McLaughlin J, Crist WM, Champlin R and Witte ON . (1987). Science, 235, 85–88.

  • Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S and Jabs EW . (1998). Genomics, 51, 468–471.

  • Garcia-Hernandez B, Castellanos A, Lopez A, Orfao A and Sanchez-Garcia I . (1997). Proc. Natl. Acad. Sci. USA, 94, 13239–13244.

  • Hajra KM, Chen DY and Fearon ER . (2002). Cancer Res., 62, 1613–1618.

  • Inoue A, Seidel MG, Wu W, Kamizono S, Ferrando AA, Bronson RT, Iwasaki H, Akashi K, Morimoto A, Hitzler JK, Pestina TI, Jackson CW, Tanaka R, Chong MJ, McKinnon PJ, Inukai T, Grosveld GC and Look AT . (2002). Cancer Cell, 2, 279–288.

  • Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, Mao M, Inaba T and Look AT . (1999). Mol. Cell, 4, 343–352.

  • Jiang R, Lan Y, Norton CR, Sundberg JP and Gridley T . (1998). Dev. Biol., 198, 277–285.

  • Khan J, Bittner ML, Saal LH, Teichmenn V, Azorsa DO, Gooden GC, Pavan WJ, Trent JM and Meltzer PS . (1999). Proc. Natl. Acad. Sci. USA, 96, 13264–13269.

  • Metcalf D . (1998). Nature, 339, 27–30.

  • Nieto MA . (2002). Nat. Rev. Mol. Cell. Biol., 3, 155–166.

  • Nieto MA, Sargent MG, Wilkinson DG and Cooke J . (1994). Science, 264, 835–839.

  • Oram KF, Carver EA and Gridley T . (2003). Anat Rec., 271A, 189–191.

  • Palacios R and Steinmetz M . (1985). Cell, 41, 727.

  • Perez-Losada J, Sanchez-Martin M, Rodriguez-Garcia A, Sanchez ML, Orfao A, Flores T and Sanchez-Garcia I . (2002). Blood, 100, 1274–1286.

  • Perez-Losada J, Sanchez-Martin M, Perez-Caro M, Perez-Mancera PA and Sanchez-Garcia I . (2003). Oncogene, 22, 4205–4211.

  • Sánchez-García I . (1997). Annu. Rev. Genet., 31, 429–453.

  • Sánchez-García I and Grütz G . (1995). Proc. Natl. Acad. Sci. USA, 92, 5287–5291.

  • Sanchez-Martin M, Gonzalez-Herrero I and Sanchez-Garcia I . (2004). Atlas Genet. Cytogenet. Oncol. Haematol. (http://www.infobiogen.fr/services/chromcancer/Genes/SNAI2ID453.html).

  • Sanchez-Martin M, Perez-Losada J, Rodriguez-Garcia A, Gonzalez-Sanchez B, Korf BR, Kuster W, Moss C, Spritz RA and Sanchez-Garcia I . (2003). Am. J. Med. Genet., 122A, 125–132.

  • Sanchez-Martin M, Rodriguez-Garcia A, Perez-Losada J, Sagrera A, Read AP and Sanchez-Garcia I . (2002). Hum. Mol. Genet., 11, 3231–3236.

  • Schultze N, Burki Y, Lang Y, Certa U and Bluethmann H . (1996). Nature Biotechnology, 14, 499–503.

  • Sefton M, Sanchez S and Nieto MA . (1998). Development, 125, 3111–3121.

  • Shtivelman E, Lifshitz B, Gale RP and Canaani E . (1985). Nature, 315, 550–554.

  • Tabernero MD, Bortoluci AM, Alaejos I, López-Berges MC, Rasillo A, García-Sanz R, García M, Sayagues JM, González M, Mateo G, San Miguel JF and Orfao A . (2001). Leukemia, 15, 1–9.

Download references

Acknowledgements

We thank all members of lab 13 for their helpful comments and constructive discussions on the manuscript. We are grateful to Dr T Gridley for the Slug mutant mice, and to Dr H Bluethmann for the Combi-tTA vector. We are also grateful to Dr A Bonati for the TOM-1 and Nalm-1 cell lines. Research in our group is supported by MEyC (BIO2000-0453-P4-02, SAF2003-01103 and FIT-010000-2004-157), Junta de Castilla y León (CSI06/03), ADE de Castilla y León (04/04/SA/0001), FIS (PI020138, G03/179, and G03/136) and USAL-CIBASA project. MPC is a recipient of an MCyT fellowship and MSM is supported by Fundación Científica de la AECC.

Author information

Author notes

  1. Pedro Antonio Pérez-Mancera and Inés González-Herrero: These authors have contributed equally to this work.

Authors and Affiliations

  1. Laboratorio 13, Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC/Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    Pedro Antonio Pérez-Mancera, Inés González-Herrero, María Pérez-Caro, Noelia Gutiérrez-Cianca, Manuel Sánchez-Martín & Isidro Sánchez-García

  2. Servicio de Anatomía Patológica, Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    Teresa Flores

  3. Area de Reproducción Animal, Centro de Investigación y Tecnología, Ctra de la Coruña km 5.9, 28040, Madrid, Spain

    Alfonso Gutiérrez-Adán & Belén Pintado

  4. Departamento de Medicina, Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    Manuel Sánchez-Martín

Authors
  1. Pedro Antonio Pérez-Mancera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inés González-Herrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Pérez-Caro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noelia Gutiérrez-Cianca
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teresa Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alfonso Gutiérrez-Adán
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Belén Pintado
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Manuel Sánchez-Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Isidro Sánchez-García
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isidro Sánchez-García.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pérez-Mancera, P., González-Herrero, I., Pérez-Caro, M. et al. SLUG in cancer development. Oncogene 24, 3073–3082 (2005). https://doi.org/10.1038/sj.onc.1208505

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208505

Keywords

This article is cited by

Search

Advanced search

Quick links