Survival Pathways of HIF-Deficient Tumour Cells: TCA Inhibition, Peroxisomal Fatty Acid Oxidation Activation and an AMPK-PGC-1α Hypoxia Sensor
Abstract
:1. Introduction
2. Materials and Method
2.1. Cell Culture
2.2. Metabolite and Enzyme Assays
2.3. 13C tracer Studies
2.4. TaqMan Gene Expression and ELISA Measurements
2.5. Data Analysis and Statistical Methods
3. Results
3.1. Hepa-1 HIF-1β-Deficient Cells Are Capable of Growth in Hypoxia
3.2. Glucose Consumption and Lactate Production Increases in Response to Hypoxia in HIF-1β-Deficient Hepa-1 Cells
3.3. Hepa-1 HIF-1β-Deficient Cells Downregulate Their TCA Cycle Flux, Shuttle Citrate out, and Channel Carbons toward Malonyl-CoA Synthesis
3.4. Hepa-1 HIF-1β-Deficient Cells Show Increased Signalling via AMPK-PPARα-PGC1α
3.5. Hepa-1 c4 Cells Show Increases in Peroxisomal Markers and PPP
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Golinska, M.A.; Stubbs, M.; Harris, A.L.; Boros, L.G.; Basetti, M.; McIntyre, D.J.O.; Griffiths, J.R. Survival Pathways of HIF-Deficient Tumour Cells: TCA Inhibition, Peroxisomal Fatty Acid Oxidation Activation and an AMPK-PGC-1α Hypoxia Sensor. Cells 2022, 11, 3595. https://doi.org/10.3390/cells11223595
Golinska MA, Stubbs M, Harris AL, Boros LG, Basetti M, McIntyre DJO, Griffiths JR. Survival Pathways of HIF-Deficient Tumour Cells: TCA Inhibition, Peroxisomal Fatty Acid Oxidation Activation and an AMPK-PGC-1α Hypoxia Sensor. Cells. 2022; 11(22):3595. https://doi.org/10.3390/cells11223595
Chicago/Turabian StyleGolinska, Monika A., Marion Stubbs, Adrian L. Harris, Laszlo G. Boros, Madhu Basetti, Dominick J. O. McIntyre, and John R. Griffiths. 2022. "Survival Pathways of HIF-Deficient Tumour Cells: TCA Inhibition, Peroxisomal Fatty Acid Oxidation Activation and an AMPK-PGC-1α Hypoxia Sensor" Cells 11, no. 22: 3595. https://doi.org/10.3390/cells11223595