Abstract
In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway. The latter phenomenon can finally lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. Having capitalized on the computational modeling, in this study, for the first time, we aimed to investigate the effects of hypoxia-induced factor-1 (HIF-1) mediated hypoxia on the magnitude of functional expression of all the enzymes and transporters involved in the glycolysis process. The main objective was to establish a quantitative relationship between the hypoxia intensity and the intracellular lactate levels and determine the key regulators of the glycolysis pathway. This model clearly showed an increase in the lactate concentration during the oxygen depletion. The proposed model also predicted that the phosphofructokinase-1 and phosphoglucomutase enzymes might play the most important roles in the regulation of the lactate production.
Highlights
In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells
This phenomenon is induced by the alterations in the functional expression and/or activity of enzymes and transporters involved in the glucose metabolism[3]
Hypoxia was introduced based on different levels of hypoxia-induced factor-1 (HIF-1)
Summary
Hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway The latter phenomenon can lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. In normal cells under the normoxic condition, about 10% of the energy requirements of the cell is provided by the glycolysis pathway, while in cancer cells and under hypoxic condition, the percentage of energy provided by the glycolysis can increase by up to 50% This phenomenon is induced by the alterations in the functional expression and/or activity of enzymes and transporters involved in the glucose metabolism[3]. To determine the key regulators of hypoxia, we aimed to establish a mathematical model to demonstrate the quantitative relationship between the oxygen availability to cells and the production of lactate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
