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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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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