A critical role of histone deacetylases, Mbd3/NuRD and Tet2 in epithelial-mesenchymal cell plasticity and in tumor invasion and metastasis

We have generated and employed reversible and irreversible EMT models of murine breast cancer cells to identify the key players establishing cell state transitions during a reversible and an irreversible EMT. We demonstrate that the Mbd3/NuRD complex, involving histone deacetylases (HDACs) and Tet2 hydroxylase, acts as an epigenetic block in epithelial-mesenchymal plasticity. These epigenetic modifiers keep breast cancer cells in a stable mesenchymal state, and their pharmacological inhibition or genetic ablation leads to a mesenchymal-epithelial transition (MET) and represses primary tumor growth and metastasis formation of highly aggressive, mesenchymal breast cancer cells. Overall design: We performed RNA-sequencing of 2 replicates of each treatment and cell line