Journal
BIOMOLECULES
Volume 12, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/biom12060762
Keywords
sigma-1 receptor; cancer metabolism; mitochondrial bioenergetics; A549; MCF7
Categories
Funding
- Austrian Science Fund (FWF) [DK-MCD W1226, P28529, I3716]
- MEFO Graz
- Nikon Austria
- Austrian Science Fund (FWF) [I3716] Funding Source: Austrian Science Fund (FWF)
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The study revealed that S1R plays an important role in cancer energy metabolism. Activation of S1R increases mitochondrial bioenergetics while reducing reliance on aerobic glycolysis in cancer cells. S1R antagonist, on the other hand, increases aerobic glycolysis in S1R expressing cancer cell line.
Sigma-1 receptor (S1R) is an important endoplasmic reticulum chaperone with various functions in health and disease. The purpose of the current work was to elucidate the involvement of S1R in cancer energy metabolism under its basal, activated, and inactivated states. For this, two cancer cell lines that differentially express S1R were treated with S1R agonist, (+)-SKF10047, and antagonist, BD1047. The effects of the agonist and antagonist on cancer energy metabolism were studied using single-cell fluorescence microscopy analysis of real-time ion and metabolite fluxes. Our experiments revealed that S1R activation by agonist increases mitochondrial bioenergetics of cancer cells while decreasing their reliance on aerobic glycolysis. S1R antagonist did not have a major impact on mitochondrial bioenergetics of tested cell lines but increased aerobic glycolysis of S1R expressing cancer cell line. Our findings suggest that S1R plays an important role in cancer energy metabolism and that S1R ligands can serve as tools to modulate it.
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