DNA methylation-driven EMT is a common mechanism of resistance to various therapeutic agents in cancer.

ABSTRACT:

Background

Overcoming therapeutic resistance is one of the major hurdles in cancer care. One mechanism contributing to therapeutic resistance is a process in which epithelial cells switch to a mesenchymal state (epithelial-to-mesenchymal transition or EMT). The precise mechanisms driving EMT-mediated therapeutic resistance have, however, not been elucidated.

Results

Here, we study ten cell line pairs, for which parental cell lines were made resistant to either a targeted or chemotherapy-based treatment. First, we show by miRNA-200 overexpression that treatment resistance is driven by EMT. Next, we demonstrate that DNA methylation changes occur within each cell line pair and show that exposure to 5-azacytidine or knock down of DNA methyltransferases (DNMTs), both of which glo

SUBMITTER: Galle E 

PROVIDER: S-EPMC7023776 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature