Epigenetic plasticity potentiates a rapid cyclical shift to and from an aggressive cancer phenotype.

ABSTRACT: Highly tumorigenic, drug-resistant cancer stem-like cells drive cancer progression. These aggressive cells can arise repeatedly from bulk tumor cells independently of mutational events, suggesting an epigenetic mechanism. To test this possibility, we studied bladder cancer cells as they cyclically shifted to and from a cancer stem-like phenotype, and we discovered that these two states exhibit distinct DNA methylation and chromatin accessibility. Most differential chromatin accessibility was independent of methylation and affected the expression of driver genes such as E2F3, a cell cycle regulator associated with aggressive bladder cancer. Cancer stem-like cells exhibited increased E2F3 promoter accessibility and increased E2F3 expression that drove cell migration, invasiveness and drug re

SUBMITTER: Xu T 

PROVIDER: S-EPMC7448727 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature