Snail blocks the cell cycle and confers resistance to cell death

  1. Sonia Vega1,
  2. Aixa V. Morales1,3,
  3. Oscar H. Ocaña1,3,
  4. Francisco Valdés2,
  5. Isabel Fabregat2, and
  6. M. Angela Nieto1,4
  1. 1Instituto Cajal, Consejo Superior de Investigaciones Cieutificas, 28002 Madrid, Spain; 2Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain

Abstract

The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis.

Keywords

Footnotes

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.294104.

  • 3 These authors contributed equally to this work.

  • 4 Corresponding author.

    4 E-MAIL anieto{at}cajal.csic.es; FAX 34-91-585-4754.

    • Accepted April 5, 2004.
    • Received December 5, 2003.
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