Back

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.

2022-08-25 cancer biology
10.1101/2022.08.23.504814 bioRxiv
Show 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.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.