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 ROSlo M-BCSCs to a ROShi 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 differentiation and cytotoxicity following suppression of NRF2 or downstream thioredoxin (TXN) and glutathione (GSH) antioxidant pathways. Co-inhibition of glycolysis and TXN and GSH pathways suppresses tumor growth, tumor-initiating potential, and metastasis by eliminating both M- and E-BCSCs. Exploiting metabolic vulnerabilities of distinct BCSC states provides a novel therapeutic approach targeting this critical tumor cell population.
Pharmacology, Toxicology and Pharmaceutical Science
5
2%
Engineering
5
2%
Other
29
11%
Unknown
96
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 49. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 July 2020.
All research outputs
#1,092,325
of 34,376,207 outputs
Outputs from Cell Metabolism (Science Direct)
#1,041
of 3,801 outputs
Outputs of similar age
#17,697
of 372,930 outputs
Outputs of similar age from Cell Metabolism (Science Direct)
#31
of 64 outputs
Altmetric has tracked 34,376,207 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,801 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 76.0. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 372,930 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 64 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
