The thermodynamic state of aerobic glycolytic flux plays a critical role in stabilizing aerobic glycolytic flux of cancer cells
Jin, C.; Hu, W.; Wang, Y.; Wu, H.; Zeng, S.; Ying, M.; Hu, X.
Show abstract
Inhibition of aerobic glycolysis (AG) is a strategy for cancer treatment, but its clinical translation has not been successful, suggesting that the mechanism underlying the inhibition of AG is not completely understood. We introduce thermodynamic state of AG (TSAG) into AG flux control, which refers the actual change of Gibbs free energy ({Delta}G) of reactions along the pathway. By using PKM2 knockdown and knockout models, we found that TSAG is resistant to PKM2 perturbation and it can effectively counteract the inhibitory effect of PKM2 perturbation on AG flux. Moreover, we deciphered the interrelationship between TSAG, AG rate, intermediate concentrations, and PK activity, revealed that TSAG is a system property of AG independent of cancer cells pathophysiological features and it plays important roles in stabilizing AG flux responding to perturbation. We propose that both inhibition of glycolytic enzyme and disruption of TSAG are required for effective AG inhibition.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multi-omic analysis of bat versus human fibroblasts reveals altered central metabolism 93%
- Metabolic heterogeneity of colorectal cancer as a prognostic factor: insights gained from fluorescence lifetime imaging 92%
- Hyperglycemia-induced cathepsin L maturation: Linking to diabetic comorbidities and COVID-19 mortality 92%
Similar papers in this journal
- Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells 95%
- Constructing an ethanol utilization pathway in Escherichia coli to produce acetyl-CoA derived compounds 92%
- Enzyme capacity-based genome scale modelling of CHO cells 92%
Similar papers in this journal
- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A 93%
- Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer 93%
- Targeting metabolic fluxes reverts metastatic transitions in ovarian cancer 92%
Similar papers in this journal
- Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle 93%
- Substrate Channeling via a Transient Protein-Protein Complex: The case of D-Glyceraldehyde-3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase 93%
- MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.