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Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition
Epithelial-mesenchymal transition (EMT), a basic developmental process that might promote cancer metastasis, has been studied from various perspectives. Recently, the early warning theory has been used to anticipate critical transitions in EMT from mathematical modeling. However, the underlying mech...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553640/ https://www.ncbi.nlm.nih.gov/pubmed/34480928 http://dx.doi.org/10.1016/j.bpj.2021.08.043 |
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author | Lang, Jintong Nie, Qing Li, Chunhe |
author_facet | Lang, Jintong Nie, Qing Li, Chunhe |
author_sort | Lang, Jintong |
collection | PubMed |
description | Epithelial-mesenchymal transition (EMT), a basic developmental process that might promote cancer metastasis, has been studied from various perspectives. Recently, the early warning theory has been used to anticipate critical transitions in EMT from mathematical modeling. However, the underlying mechanisms of EMT involving complex molecular networks remain to be clarified. Especially, how to quantify the global stability and stochastic transition dynamics of EMT and what the underlying mechanism for early warning theory in EMT is remain to be fully clarified. To address these issues, we constructed a comprehensive gene regulatory network model for EMT and quantified the corresponding potential landscape. The landscape for EMT displays multiple stable attractors, which correspond to E, M, and some other intermediate states. Based on the path-integral approach, we identified the most probable transition paths of EMT, which are supported by experimental data. Correspondingly, the results of transition actions demonstrated that intermediate states can accelerate EMT, consistent with recent studies. By integrating the landscape and path with early warning concept, we identified the potential barrier height from the landscape as a global and more accurate measure for early warning signals to predict critical transitions in EMT. The landscape results also provide an intuitive and quantitative explanation for the early warning theory. Overall, the landscape and path results advance our mechanistic understanding of dynamical transitions and roles of intermediate states in EMT, and the potential barrier height provides a new, to our knowledge, measure for critical transitions and quantitative explanations for the early warning theory. |
format | Online Article Text |
id | pubmed-8553640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-85536402022-10-19 Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition Lang, Jintong Nie, Qing Li, Chunhe Biophys J Articles Epithelial-mesenchymal transition (EMT), a basic developmental process that might promote cancer metastasis, has been studied from various perspectives. Recently, the early warning theory has been used to anticipate critical transitions in EMT from mathematical modeling. However, the underlying mechanisms of EMT involving complex molecular networks remain to be clarified. Especially, how to quantify the global stability and stochastic transition dynamics of EMT and what the underlying mechanism for early warning theory in EMT is remain to be fully clarified. To address these issues, we constructed a comprehensive gene regulatory network model for EMT and quantified the corresponding potential landscape. The landscape for EMT displays multiple stable attractors, which correspond to E, M, and some other intermediate states. Based on the path-integral approach, we identified the most probable transition paths of EMT, which are supported by experimental data. Correspondingly, the results of transition actions demonstrated that intermediate states can accelerate EMT, consistent with recent studies. By integrating the landscape and path with early warning concept, we identified the potential barrier height from the landscape as a global and more accurate measure for early warning signals to predict critical transitions in EMT. The landscape results also provide an intuitive and quantitative explanation for the early warning theory. Overall, the landscape and path results advance our mechanistic understanding of dynamical transitions and roles of intermediate states in EMT, and the potential barrier height provides a new, to our knowledge, measure for critical transitions and quantitative explanations for the early warning theory. The Biophysical Society 2021-10-19 2021-09-02 /pmc/articles/PMC8553640/ /pubmed/34480928 http://dx.doi.org/10.1016/j.bpj.2021.08.043 Text en © 2021 Biophysical Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Lang, Jintong Nie, Qing Li, Chunhe Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title | Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title_full | Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title_fullStr | Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title_full_unstemmed | Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title_short | Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
title_sort | landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553640/ https://www.ncbi.nlm.nih.gov/pubmed/34480928 http://dx.doi.org/10.1016/j.bpj.2021.08.043 |
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