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NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype

Jia, W and Jolly, MK and Levine, H (2022) NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype. In: Frontiers in Cell and Developmental Biology, 9 .

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Official URL: https://doi.org/10.3389/fcell.2021.828250


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. Copyright © 2022 Jia, Jolly and Levine.

Item Type: Journal Article
Publication: Frontiers in Cell and Developmental Biology
Publisher: Frontiers Media S.A.
Additional Information: The copyright for this article belongs to Authors
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 14 Feb 2022 15:37
Last Modified: 14 Feb 2022 15:37
URI: http://eprints.iisc.ac.in/id/eprint/71331

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