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

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dc.citation.articleNumber828250
dc.citation.journalTitleFrontiers in Cell and Developmental Biology
dc.citation.volumeNumber9
dc.contributor.authorJia, Wen
dc.contributor.authorJolly, Mohit Kumar
dc.contributor.authorLevine, Herbert
dc.date.accessioned2022-03-24T13:31:40Z
dc.date.available2022-03-24T13:31:40Z
dc.date.issued2022
dc.description.abstractThe 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.
dc.identifier.citationJia, Wen, Jolly, Mohit Kumar and Levine, Herbert. "NRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype." <i>Frontiers in Cell and Developmental Biology,</i> 9, (2022) Frontiers Media S.A.: https://doi.org/10.3389/fcell.2021.828250.
dc.identifier.digitalfcell-09-828250
dc.identifier.doihttps://doi.org/10.3389/fcell.2021.828250
dc.identifier.urihttps://hdl.handle.net/1911/112042
dc.language.isoeng
dc.publisherFrontiers Media S.A.
dc.rightsThis 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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleNRF2-dependent Epigenetic Regulation can Promote the Hybrid Epithelial/Mesenchymal Phenotype
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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