Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence

Stéphane Ansieau, Jeremy Bastid, Agnès Doreau, Anne Pierre Morel, Benjamin P. Bouchet, Clémence Thomas, Frédérique Fauvet, Isabelle Puisieux, Claudio Doglioni, Sara Piccinin, Roberta Maestro, Thibault Voeltzel, Abdelkader Selmi, Sandrine Valsesia-Wittmann, Claude Caron de Fromentel, Alain Puisieux

Research output: Contribution to journalArticle

Abstract

Twist1 and Twist2 are major regulators of embryogenesis. Twist1 has been shown to favor the metastatic dissemination of cancer cells through its ability to induce an epithelial-mesenchymal transition (EMT). Here, we show that a large fraction of human cancers overexpress Twist1 and/or Twist2. Both proteins override oncogene-induced premature senescence by abrogating key regulators of the p53- and Rb-dependent pathways. Twist1 and Twist2 cooperate with Ras to transform mouse embryonic fibroblasts. Interestingly, in epithelial cells, the oncogenic cooperation between Twist proteins and activated mitogenic oncoproteins, such as Ras or ErbB2, leads to complete EMT. These findings suggest an unanticipated direct link between early escape from failsafe programs and the acquisition of invasive features by cancer cells.

Original languageEnglish
Pages (from-to)79-89
Number of pages11
JournalCancer Cell
Volume14
Issue number1
DOIs
Publication statusPublished - Jul 8 2008

Keywords

  • CELLBIO
  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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  • Cite this

    Ansieau, S., Bastid, J., Doreau, A., Morel, A. P., Bouchet, B. P., Thomas, C., Fauvet, F., Puisieux, I., Doglioni, C., Piccinin, S., Maestro, R., Voeltzel, T., Selmi, A., Valsesia-Wittmann, S., Caron de Fromentel, C., & Puisieux, A. (2008). Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence. Cancer Cell, 14(1), 79-89. https://doi.org/10.1016/j.ccr.2008.06.005