Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence
Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence
复制标题
DOI：
10.1016/j.ccr.2008.06.005
复制
发表时间：
2008-07-01
期刊：
影响因子：
50.3
通讯作者：
Puisieux, Alain
中科院分区：
文献类型：
--
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
Twist1和Twist2是胚胎发生的主要调控因子。Twist1通过诱导上皮-间质转化（epithelial-mesenchymal transition， EMT）的能力，被证明有利于癌细胞的转移传播。在这里，我们发现大部分人类癌症过表达Twist1和/或Twist2。这两种蛋白通过废除p53和rb依赖通路的关键调节因子来覆盖癌基因诱导的过早衰老。Twist1和Twist2与Ras协同转化小鼠胚胎成纤维细胞。有趣的是，在上皮细胞中，Twist蛋白和活化的有丝分裂癌蛋白（如Ras或ErbB2）之间的致癌合作导致了完全的EMT。这些发现表明，早期逃离故障安全程序与癌细胞获得侵袭性特征之间存在意想不到的直接联系。
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.