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bioRxiv · 10.1101/2022.08.23.504814

Epigenetic memory acquired during long-term EMTinduction governs the recovery to the epithelial state

Jain, P.·Corbo, S.·Mohammad, K.·George, J. T.·Levine, H.·Toneff, M. J.·Jolly, M. K.
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Abstract

Epithelial-Mesenchymal Transition (EMT) and its reverse Mesenchymal-Epithelial Transition (MET) are critical during embryonic development, wound healing and cancer metastasis. While phenotypic changes during short-term EMT induction are reversible, long-term EMT induction has been often associated with irreversibility. Here, we show that phenotypic changes seen in MCF10A cells upon long-term EMT induction by TGF{beta} need not be irreversible, but have relatively longer timescales of reversibility than those seen in short-term induction. Next, using a phenomenological mathematical model incorporating the epigenetic silencing of miR-200 by ZEB, we highlight how the epigenetic memory gained during long-term EMT induction can slow the recovery to the epithelial state post-TGF{beta} withdrawal. Our results suggest that epigenetic modifiers can govern the extent and timescale of EMT reversibility, and advise caution against labelling phenotypic changes seen in long-term EMT induction as irreversible.

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Jain, P., Corbo, S., Mohammad, K., George, J. T., Levine, H., Toneff, M. J., Jolly, M. K.. 2022-08-25. Epigenetic memory acquired during long-term EMTinduction governs the recovery to the epithelial state. https://doi.org/10.1101/2022.08.23.504814

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