Anniversary Lecture

Epithelial plasticity in health and disease

Prof. Angela Nieto

Epithelial homeostasis is crucial to maintain tissue architecture, and therefore, it needs to be tightly regulated in the adult. By contrast, embryonic cells show a high degree of epithelial plasticity required for proper morphogenesis and, in particular, for the implementation of massive cell movements that occur during gastrulation and neural crest delamination among other processes. We have been interested in the analysis of cell movements, plasticity and epithelial to mesenchymal transitions (EMT) for many years, and found that the reactivation of developmental EMT-like programs in adult cells leads to several pathologies including tumor progression and organ degeneration. While the epithelial and mesenchymal cells are usually considered as extreme phenotypes, intermediate EMT states also exist. Under those circumstances cells depict a hybrid phenotype expressing both epithelial and mesenchymal markers and from which they can reverse to the original state or move towards a more mesenchymal phenotype. Hybrid transitory states can favor coordinated cell migration or wound healing but they can also enable the formation of clusters of migratory cancer cells with increased tumor initiating potential. However, in contrast to the situation in cancer, the intermediate phenotype holds promise for new antifibrotic therapeutic approaches, as inhibiting EMT can attenuate established fibrosis. I will discuss different scenarios in which this intermediate phenotype is observed both in development and in disease, and will also refer to a new developmental EMT that we have found to be crucial for heart laterality and morphogenesis in vertebrates.