Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence
| Autor: | Frédérique Fauvet, Agnès Doreau, Thibault Voeltzel, Abdelkader Selmi, Claude Caron de Fromentel, Benjamin Pierre Bouchet, Stéphane Ansieau, Alain Puisieux, Roberta Maestro, Claudio Doglioni, Clémence Thomas, Isabelle Puisieux, Sara Piccinin, Jérémy Bastid, Anne Pierre Morel, Sandrine Valsesia-Wittmann |
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| Přispěvatelé: | Ansieau, Stephane, Bastid, Jeremy, Doreau, Agne, Morel Anne, Pierre, Bouchet Benjamin, P., Thomas, Clemence, Fauvet, Frederique, Puisieux, Isabelle, Doglioni, Claudio, Piccinin, Sara, Maestro, Roberta, Voeltzel, Thibault, Selmi, Abdelkader, Valsesia Wittmann, Sandrine, de Fromentel Claude, Caron, Puisieux, Alain |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
animal structures Transplantation Heterologous HUMDISEASE Mice Nude Mice Transgenic Biology Transfection Retinoblastoma Protein Cell Line Mice Twist transcription factor Dogs Downregulation and upregulation Neoplasms Animals Humans Neoplasm Invasiveness Mammary Glands Human Cellular Senescence Regulation of gene expression Twist-Related Protein 1 Nuclear Proteins Epithelial Cells Cell Biology Fibroblasts Embryonic stem cell Up-Regulation Cell biology Enzyme Activation Gene Expression Regulation Neoplastic Mice Inbred C57BL Repressor Proteins Transplantation Cell Transformation Neoplastic Oncology Mice Inbred DBA SIGNALING Cell culture Cell Transdifferentiation Cancer cell Immunology ras Proteins RNA Interference CELLBIO Tumor Suppressor Protein p53 |
| Zdroj: | Cancer Cell. 14:79-89 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2008.06.005 |
| Popis: | SummaryTwist1 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. |
| Databáze: | OpenAIRE |
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