Complex landscape of the epithelial-mesenchymal transition

Cells can change their phenotype from epithelial to mesenchymal during development and in cancer progression, where this transition is often associated with metastasis and poor disease prognosis. We simulate a Boolean network model of the pathway regulating the epithelial–mesenchymal transition, reconstruct its complex phenotypic landscape and validate it by analyzing single cell transcriptomic data. The statistical features of the landscape are similar to those found in the free energy of glassy materials and suggest that highly aggressive hybrid epithelial/mesenchymal cell phenotypes are located in metastable regions that can easily switch under external and internal perturbations. We thus propose a general mapping strategy for gene regulatory networks that can be used to visualize the ever increasing number of gene expression data obtained from single cells and tissues.

F. Font Clos, S. Zapperi, C. A. M. La Porta, PNAS 115, 5902 (2018)