> Detailanzeige

Totten, Stephanie P.; Im, Young Kyuen; Cepeda Cañedo, Eduardo; Najyb, Ouafa; Nguyen, Alice; Hébert, Steven; Ahn, Ryuhjin; Lewis, Kyle; Lebeau, Benjamin; La Selva, Rachel; Sabourin, Valérie; Martínez, Constanza; Savage, Paul; Kuasne, Hellen; Avizonis, Daina; Santos Martínez, Nancy; Chabot, Catherine; Aguilar-Mahecha, Adriana; Goulet, Marie-Line; Dankner, Matthew; Witcher, Michael; Petrecca, Kevin; Basik, Mark; Pollak, Michael; [...]

STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer
  • Beteiligte: Totten, Stephanie P.; Im, Young Kyuen; Cepeda Cañedo, Eduardo; Najyb, Ouafa; Nguyen, Alice; Hébert, Steven; Ahn, Ryuhjin; Lewis, Kyle; Lebeau, Benjamin; La Selva, Rachel; Sabourin, Valérie; Martínez, Constanza; Savage, Paul; Kuasne, Hellen; Avizonis, Daina; Santos Martínez, Nancy; Chabot, Catherine; Aguilar-Mahecha, Adriana; Goulet, Marie-Line; Dankner, Matthew; Witcher, Michael; Petrecca, Kevin; Basik, Mark; Pollak, Michael; [...]
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-021-23396-2
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.</jats:p>
  • Zugangsstatus: Freier Zugang