Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence

Stéphane Ansieau; Jeremy Bastid; Agnès Doreau; Anne-Pierre Morel; Benjamin P 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

doi:10.1016/j.ccr.2008.06.005

Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence

Cancer Cell. 2008 Jul 8;14(1):79-89. doi: 10.1016/j.ccr.2008.06.005.

Authors

Stéphane Ansieau¹, Jeremy Bastid, Agnès Doreau, Anne-Pierre Morel, Benjamin P 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

Affiliation

¹ Inserm, U590, Lyon F-69008, France.

PMID: 18598946
DOI: 10.1016/j.ccr.2008.06.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Transdifferentiation* / genetics
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism*
Cell Transformation, Neoplastic / pathology
Cellular Senescence* / genetics
Dogs
Enzyme Activation
Epithelial Cells / enzymology
Epithelial Cells / metabolism*
Epithelial Cells / pathology
Fibroblasts / enzymology
Fibroblasts / metabolism*
Fibroblasts / pathology
Gene Expression Regulation, Neoplastic
Humans
Mammary Glands, Human / metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Nude
Mice, Transgenic
Neoplasm Invasiveness
Neoplasms / enzymology
Neoplasms / genetics
Neoplasms / metabolism*
Neoplasms / pathology
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
RNA Interference
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Retinoblastoma Protein / metabolism
Transfection
Transplantation, Heterologous
Tumor Suppressor Protein p53 / metabolism
Twist-Related Protein 1 / genetics
Twist-Related Protein 1 / metabolism*
Up-Regulation
ras Proteins / metabolism

Substances

Nuclear Proteins
Repressor Proteins
Retinoblastoma Protein
TWIST1 protein, human
TWIST2 protein, human
Tumor Suppressor Protein p53
Twist-Related Protein 1
ras Proteins

Associated data

GEO/GSE11756