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Sigma-1 Receptor Modulation by Ligands Coordinates Cancer Cell Energy Metabolism.
Furkan E Oflaz1, Zhanat Koshenov1, Martin Hirtl1
1Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.
Biomolecules
|June 24, 2022
Summary
Sigma-1 receptor (S1R) activation boosts cancer cell mitochondrial energy production and reduces glycolysis. S1R ligands may offer new ways to target cancer metabolism.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- The sigma-1 receptor (S1R) is a key endoplasmic reticulum chaperone involved in cellular functions.
- S1R's role in cancer energy metabolism, particularly under different activation states, requires further elucidation.
Purpose of the Study:
- To investigate the involvement of S1R in cancer cell energy metabolism.
- To determine how S1R activation and inactivation influence mitochondrial bioenergetics and glycolysis.
Main Methods:
- Utilized two cancer cell lines with differential S1R expression.
- Administered S1R agonist ((+)-SKF10047) and antagonist (BD1047).
- Analyzed real-time ion and metabolite fluxes using single-cell fluorescence microscopy.
Main Results:
- S1R activation by agonist enhanced mitochondrial bioenergetics in cancer cells.
- S1R activation decreased cancer cell reliance on aerobic glycolysis.
- S1R antagonist showed minimal impact on mitochondrial bioenergetics but increased aerobic glycolysis in S1R-expressing cells.
Conclusions:
- S1R significantly influences cancer cell energy metabolism.
- S1R ligands can be employed as tools to modulate cancer metabolism, offering potential therapeutic avenues.
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