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NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype
The epithelial-mesenchymal transition (EMT) is a cellular process critical for wound healing, cancer metastasis and embryonic development. Recent efforts have identified the role of hybrid epithelial/mesenchymal states, having both epithelial and mesehncymal traits, in enabling cancer metastasis and...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803900/ https://www.ncbi.nlm.nih.gov/pubmed/35118079 http://dx.doi.org/10.3389/fcell.2021.828250 |
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author | Jia, Wen Jolly, Mohit Kumar Levine, Herbert |
author_facet | Jia, Wen Jolly, Mohit Kumar Levine, Herbert |
author_sort | Jia, Wen |
collection | PubMed |
description | The epithelial-mesenchymal transition (EMT) is a cellular process critical for wound healing, cancer metastasis and embryonic development. Recent efforts have identified the role of hybrid epithelial/mesenchymal states, having both epithelial and mesehncymal traits, in enabling cancer metastasis and resistance to various therapies. Also, previous work has suggested that NRF2 can act as phenotypic stability factor to help stablize such hybrid states. Here, we incorporate a phenomenological epigenetic feedback effect into our previous computational model for EMT signaling. We show that this type of feedback can stabilize the hybrid state as compared to the fully mesenchymal phenotype if NRF2 can influence SNAIL at an epigenetic level, as this link makes transitions out of hybrid state more difficult. However, epigenetic regulation on other NRF2-related links do not significantly change the EMT dynamics. Finally, we considered possible cell division effects in our epigenetic regulation model, and our results indicate that the degree of epigenetic inheritance does not appear to be a critical factor for the hybrid E/M state stabilizing behavior of NRF2. |
format | Online Article Text |
id | pubmed-8803900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88039002022-02-02 NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype Jia, Wen Jolly, Mohit Kumar Levine, Herbert Front Cell Dev Biol Cell and Developmental Biology The epithelial-mesenchymal transition (EMT) is a cellular process critical for wound healing, cancer metastasis and embryonic development. Recent efforts have identified the role of hybrid epithelial/mesenchymal states, having both epithelial and mesehncymal traits, in enabling cancer metastasis and resistance to various therapies. Also, previous work has suggested that NRF2 can act as phenotypic stability factor to help stablize such hybrid states. Here, we incorporate a phenomenological epigenetic feedback effect into our previous computational model for EMT signaling. We show that this type of feedback can stabilize the hybrid state as compared to the fully mesenchymal phenotype if NRF2 can influence SNAIL at an epigenetic level, as this link makes transitions out of hybrid state more difficult. However, epigenetic regulation on other NRF2-related links do not significantly change the EMT dynamics. Finally, we considered possible cell division effects in our epigenetic regulation model, and our results indicate that the degree of epigenetic inheritance does not appear to be a critical factor for the hybrid E/M state stabilizing behavior of NRF2. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8803900/ /pubmed/35118079 http://dx.doi.org/10.3389/fcell.2021.828250 Text en Copyright © 2022 Jia, Jolly and Levine. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Jia, Wen Jolly, Mohit Kumar Levine, Herbert NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title | NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title_full | NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title_fullStr | NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title_full_unstemmed | NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title_short | NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype |
title_sort | nrf2-dependent epigenetic regulation can promote the hybrid epithelial/mesenchymal phenotype |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803900/ https://www.ncbi.nlm.nih.gov/pubmed/35118079 http://dx.doi.org/10.3389/fcell.2021.828250 |
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