Epigenetic control of epithelial-to-mesenchymal transition and cancer metastasis

Epithelial-mesenchymal transition (EMT) is vital for morphogenesis during embryonic development and is also critical for the conversion of early stage tumors into invasive malignancies. Several key inducers of EMT are transcription factors that repress the expression of E-cadherin, whose loss is a hallmark of EMT. Epigenetic regulation encompasses three types of changes: DNA methylation, histone modifications, and microRNAs, each of which has been shown to play a key role in controlling epithelial-mesenchymal transition and cancer metastasis. As we gain deeper understanding of epigenetic mechanisms controlling EMT processes and orchestrating all the metastatic steps, we broaden the therapeutic potentials of epigenetic drugs, such as DNA demethylating drugs and histone deacetylase/demethylase inhibitors, which can act upon metastasis-related genes, restoring their expression and biological functions. (c) 2012 Elsevier Inc. All rights reserved.