Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling.

ABSTRACT: Although breast cancer stem cells (BCSCs) display plasticity transitioning between quiescent mesenchymal-like (M) and proliferative epithelial-like (E) states, how this plasticity is regulated by metabolic or oxidative stress remains poorly understood. Here, we show that M- and E-BCSCs rely on distinct metabolic pathways and display markedly different sensitivities to inhibitors of glycolysis and redox metabolism. Metabolic or oxidative stress generated by 2DG, H₂O₂, or hypoxia promotes the transition of ROS^lo M-BCSCs to a ROS^hi E-state. This transition is reversed by N-acetylcysteine and mediated by activation of the AMPK-HIF1α axis. Moreover, E-BCSCs exhibit robust NRF2-mediated antioxidant responses, rendering them vulnerable to ROS-induced di

SUBMITTER: Luo M 

PROVIDER: S-EPMC6037414 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature