Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state. Academic Article uri icon

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 need not be irreversible, but have relatively longer time scales of reversibility than those seen in short-term induction. Next, using a phenomenological mathematical model to account for the chromatin-mediated epigenetic silencing of the miR-200 family by ZEB family, we highlight how the epigenetic memory gained during long-term EMT induction can slow the recovery to the epithelial state post-TGF withdrawal. Our results suggest that epigenetic modifiers can govern the extent and time scale of EMT reversibility and advise caution against labelling phenotypic changes seen in long-term EMT induction as 'irreversible'.

published proceedings

  • J R Soc Interface

altmetric score

  • 4.3

author list (cited authors)

  • Jain, P., Corbo, S., Mohammad, K., Sahoo, S., Ranganathan, S., George, J. T., ... Jolly, M. K.

citation count

  • 4

complete list of authors

  • Jain, Paras||Corbo, Sophia||Mohammad, Kulsoom||Sahoo, Sarthak||Ranganathan, Santhalakshmi||George, Jason T||Levine, Herbert||Taube, Joseph||Toneff, Michael||Jolly, Mohit Kumar

publication date

  • January 2023