Fig. 5
Epigenetic plasticity as a driver of cancer stemness. A number of plasticity programs sustain cancer stem cell (CSC) properties and tumor evolution through epigenetic mechanisms. These programs promote: (1) dedifferentiation to a stem-like state, whereby differentiated cancer cells revert to CSCs in response to oncogenic or environmental cues, including therapy, via chromatin remodeling and activation of pluripotency-associated transcriptional networks; (2) drug-tolerant persistence, in which a subpopulation of cancer cells survives therapy by entering a slow-cycling, stem-like state, forming a reservoir that seeds for relapse and resistance; (3) epithelial‒mesenchymal plasticity (EMP), referring to reversible transitions across hybrid epithelial‒mesenchymal transition (EMT) and mesenchymal‒epithelial transition (MET) states associated with stem‒like traits and increased metastatic potential; and (4) CSC heterogeneity, referring to the dynamic transitions across CSC states, contributing to tumor heterogeneity and adaptation
