Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence
2008; Cell Press; Volume: 14; Issue: 1 Linguagem: Inglês
10.1016/j.ccr.2008.06.005
ISSN1878-3686
AutoresStéphane Ansieau, Jérémy Bastid, Agnès Doreau, Anne-Pierre Morel, Benjamin Pierre 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,
Tópico(s)Genomics and Chromatin Dynamics
ResumoTwist1 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.
Referência(s)