Nature Communications (Jun 2021)

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

  • Stephanie P. Totten,
  • Young Kyuen Im,
  • Eduardo Cepeda Cañedo,
  • Ouafa Najyb,
  • Alice Nguyen,
  • Steven Hébert,
  • Ryuhjin Ahn,
  • Kyle Lewis,
  • Benjamin Lebeau,
  • Rachel La Selva,
  • Valérie Sabourin,
  • Constanza Martínez,
  • Paul Savage,
  • Hellen Kuasne,
  • Daina Avizonis,
  • Nancy Santos Martínez,
  • Catherine Chabot,
  • Adriana Aguilar-Mahecha,
  • Marie-Line Goulet,
  • Matthew Dankner,
  • Michael Witcher,
  • Kevin Petrecca,
  • Mark Basik,
  • Michael Pollak,
  • Ivan Topisirovic,
  • Rongtuan Lin,
  • Peter M. Siegel,
  • Claudia L. Kleinman,
  • Morag Park,
  • Julie St-Pierre,
  • Josie Ursini-Siegel

DOI
https://doi.org/10.1038/s41467-021-23396-2
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 20

Abstract

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Complex I inhibition induces oxidative stress leading to cancer cell cytotoxicity. Here, the authors show, in breast cancer models, that inflammatory mediators can potentiate complex I inhibitor phenformin cytotoxicity through STAT1-mediated downregulation of the reactive oxygen species scavenger NQO1.