Glioblastoma stem cells resist cuproptosis with circadian variation of copper levels
University of Pittsburgh · UPMC Hillman Cancer Center · +3 more institutions
Abstract
Cuproptosis involves accumulation of intracellular copper that triggers mitochondrial lipoylated protein aggregation and destabilization of iron-sulfur cluster proteins, leading to cell death. Pharmacologic induction of cuproptosis has been proposed as a cancer therapy. Here, we find that glioblastoma (GBM) stem cells (GSCs) displayed relative resistance to cuproptosis with circadian variation of intracellular copper levels. CRISPR screening of copper regulators under concurrent treatment with copper ionophore or clock disruption revealed dependency on ATPase copper transporting alpha (ATP7A). Circadian control of copper homeostasis was mediated by the core clock transcription factor, brain and muscle…
Citation impact
- FWCI
- 68.29
- Percentile
- 100%
- References
- 0
Authors
17- FYFanen YuanCorresponding
University of Pittsburgh, UPMC Hillman Cancer Center
- XWXujia Wu
UPMC Hillman Cancer Center
- HYHuairui Yuan
UPMC Hillman Cancer Center
- DWDonghai Wang
University of North Carolina at Chapel Hill, UPMC Hillman Cancer Center, UNC Lineberger Comprehensive Cancer Center
- THTengfei Huang
University of North Carolina at Chapel Hill, UPMC Hillman Cancer Center, UNC Lineberger Comprehensive Cancer Center
Topics & keywords
- Circadian clock
- Circadian rhythm
- Copper deficiency
- ATP7A
- Intracellular
- Stem cell
- Copper
- Metabolism