title: Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence.
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.
authors.affiliation: Inserm, U590, Lyon F-69008, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ansieau
authors.forename: Jeremy
authors.initials: J
authors.lastname: Bastid
authors.forename: Agnès
authors.initials: A
authors.lastname: Doreau
authors.forename: Anne-Pierre
authors.initials: AP
authors.lastname: Morel
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Bouchet
authors.forename: Clémence
authors.initials: C
authors.lastname: Thomas
authors.forename: Frédérique
authors.initials: F
authors.lastname: Fauvet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Puisieux
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Sara
authors.initials: S
authors.lastname: Piccinin
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestro
authors.forename: Thibault
authors.initials: T
authors.lastname: Voeltzel
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Selmi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Valsesia-Wittmann
authors.forename: Claude
authors.initials: C
authors.lastname: Caron de Fromentel
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
mesh_terms: D000818:Animals; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence / Q000235:genetics; D004285:Dogs; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; D018631:ras Proteins