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

Overview of attention for article published in Cell Metabolism (Science Direct), July 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • Good Attention Score compared to outputs of the same age and source (65th percentile)

Mentioned by

news
6 news outlets
twitter
19 tweeters
Title
Targeting Breast Cancer Stem Cell State Equilibrium through Modulation of Redox Signaling
Published in
Cell Metabolism (Science Direct), July 2018
DOI 10.1016/j.cmet.2018.06.006
Pubmed ID
Authors

Luo, Ming, Shang, Li, Brooks, Michael D., Jiagge, Evelyn, Zhu, Yongyou, Buschhaus, Johanna M., Conley, Sarah, Fath, Melissa A., Davis, April, Gheordunescu, Elizabeth, Wang, Yongfang, Harouaka, Ramdane, Lozier, Ann, Triner, Daniel, McDermott, Sean, Merajver, Sofia D., Luker, Gary D., Spitz, Douglas R., Wicha, Max S., Ming Luo, Li Shang, Michael D. Brooks, Evelyn Jiagge, Yongyou Zhu, Johanna M. Buschhaus, Sarah Conley, Melissa A. Fath, April Davis, Elizabeth Gheordunescu, Yongfang Wang, Ramdane Harouaka, Ann Lozier, Daniel Triner, Sean McDermott, Sofia D. Merajver, Gary D. Luker, Douglas R. Spitz, Max S. Wicha

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 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.

Twitter Demographics

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Attention Score in Context

This research output has an Altmetric Attention Score of 54. 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 20 July 2018.
All research outputs
#235,413
of 11,498,576 outputs
Outputs from Cell Metabolism (Science Direct)
#309
of 1,901 outputs
Outputs of similar age
#6,826
of 153,650 outputs
Outputs of similar age from Cell Metabolism (Science Direct)
#14
of 41 outputs
Altmetric has tracked 11,498,576 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,901 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 42.9. This one has done well, scoring higher than 83% 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 153,650 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 41 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 65% of its contemporaries.