The propensity for epithelial-mesenchymal transitions is dictated by chromatin states in the cancer cell of origin

At its core, epithelial-mesenchymal transition (EMT) programs are well-established physiological processes that transpire during embryogenesis to facilitate the development of the mesoderm and neural crest, and during adulthood to oversee the repair of wounded tissues (1-3). Epithelial cells undergoing EMT programs downregulate epithelial markers (e.g., E-cadherin) and upregulate mesenchymal markers (e.g., vimentin), leading to stark changes in cell morphology and behavior. For instance, epithelial cells are typically arranged as a single layer of polarized cells that exhibit strong cell-cell contacts, a phenotype that gives way during EMT programs to the generation of apolar mesenchymal-like cells that exhibit elongated spindle morphologies (1-3). Importantly, the phenomenon of EMT can be hijacked by pathological processes, including fibrosis, inflammatory conditions, and the progression and metastasis of solid tumors (1).