Analysis of a reduced model of epithelial-mesenchymal fate determination in cancer metastasis as a singularly-perturbed monotone system
From MaRDI portal
Publication:5049252
Abstract: Tumor metastasis is one of the main factors responsible for the high fatality rate of cancer. Metastasis can occur after malignant cells transition from the epithelial phenotype to the mesenchymal phenotype. This transformation allows cells to migrate via the circulatory system and subsequently settle in distant organs after undergoing the reverse transition from the mesenchymal to the epithelial phenotypes. The core gene regulatory network controlling these transitions consists of a system made up of coupled SNAIL/miRNA-34 and ZEB1/miRNA-200 subsystems. In this work, we formulate a mathematical model of the core regulatory motif and analyze its long-term behavior. We start by developing a detailed reaction network with 24 state variables. Assuming fast promoter and mRNA kinetics, we then show how to reduce our model to a monotone four-dimensional system. For the reduced system, monotone dynamical systems theory can be used to prove generic convergence to the set of equilibria for all bounded trajectories. The theory does not apply to the full model, which is not monotone, but we briefly discuss results for singularly-perturbed monotone systems that provide a tool to extend convergence results from reduced to full systems, under appropriate time separation assumptions.
Recommendations
- A mathematical insight in the epithelial-mesenchymal-like transition in cancer cells and its effect in the invasion of the extracellular matrix
- Pattern formation in a nonlocal mathematical model for the multiple roles of the TGF-\(\beta\) pathway in tumour dynamics
- When a collective outcome triggers a rare individual event: A mode of metastatic process in a cell population
- Controlling stochasticity in epithelial-mesenchymal transition through multiple intermediate cellular states
- A multiscale approach to the migration of cancer stem cells: mathematical modelling and simulations
Cites work
- An introduction to systems biology. Design principles of biological circuits.
- Differential equations and convergence almost everywhere in strongly monotone semiflows
- Geometric singular perturbation theory for ordinary differential equations
- Graph-theoretic characterizations of monotonicity of chemical networks in reaction coordinates
- scientific article; zbMATH DE number 44637 (Why is no real title available?)
- scientific article; zbMATH DE number 734901 (Why is no real title available?)
- scientific article; zbMATH DE number 1376974 (Why is no real title available?)
- scientific article; zbMATH DE number 758785 (Why is no real title available?)
- scientific article; zbMATH DE number 799793 (Why is no real title available?)
- scientific article; zbMATH DE number 2247510 (Why is no real title available?)
- scientific article; zbMATH DE number 3075094 (Why is no real title available?)
- Singularly perturbed monotone systems and an Application to double phosphorylation cycles
- Stability and convergence in strongly monotone dynamical systems.
- Systems of Differential Equations that are Competitive or Cooperative II: Convergence Almost Everywhere
Cited in
(3)
This page was built for publication: Analysis of a reduced model of epithelial-mesenchymal fate determination in cancer metastasis as a singularly-perturbed monotone system
Report a bug (only for logged in users!)Click here to report a bug for this page (MaRDI item Q5049252)
