title: Modulation of oxidative stress by twist oncoproteins.
abstract: Expression of developmental genes Twist1 and Twist2 is reactivated in many human tumors. Among their oncogenic activities, induction of epithelial to mesenchymal transition is believed to increase cell motility and invasiveness and may be related to acquisition of cancer stem cell phenotype. In addition, Twist proteins promote malignant conversion by overriding two oncogene-induced failsafe programs: senescence and apoptosis. Reactive oxygen species (ROS) are also important mediators of apoptosis, senescence and motility and are tightly linked to disease, notably to cancer. We report here that Twist factors and ROS are functionally linked. In wild type cells both Twist1 and Twist2 exhibit antioxidant properties. We show that Twist-driven modulation of oncogene-induced apoptosis is linked to its effects on oxidative stress. Finally, we identify several targets that mediate Twist antioxidant activity. These findings unveil a new function of Twist factors that could be important in explaining their pleiotropic role during carcinogenesis.
authors: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 5535, Montpellier, France.
authors: Nicolas
authors: N
authors: Floc'h
authors: Jakub
authors: J
authors: Kolodziejski
authors: Leila
authors: L
authors: Akkari
authors: Yannick
authors: Y
authors: Simonin
authors: Stéphane
authors: S
authors: Ansieau
authors: Alain
authors: A
authors: Puisieux
authors: Urszula
authors: U
authors: Hibner
authors: Patrice
authors: P
authors: Lassus
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1
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