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