The Quantitative Analysis of Dynamic Mechanisms Impacting Gastric Cancer Cell Proliferation via Serine/glycine Conversion
Objective Gastric cancer(GC)seriously affects human health and life,and research has shown that it is closely related to the serine/glycine metabolism.The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine.The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells.Methods In this work,a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems.Based on the regulation of the model,a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells.We introduced random noise to the kinetic equations of the general metabolic network,and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space.A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations.Results Despite the unavailability of a large number of dynamic parameters,we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells.When extracellular serine is available,the model preferentially consumes serine.In addition,when the conversion rate of glycine to serine increases,the model significantly upregulates the steady-state fluxes of S-adenosylmethionine(SAM)and S-adenosyl homocysteine(SAH).Conclusion In this paper,we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation,which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process.This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.
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