Epigenetic regulation of hybrid epithelial-mesenchymal cell states in cancer

Epithelial-to-mesenchymal transition (EMT) is a process by which cells lose their epithelial characteristics and gain mesenchymal phenotypes. In cancer, EMT is thought to drive tumor invasion and metastasis. Recent efforts to understand EMT biology have uncovered that cells undergoing EMT attain a spectrum of intermediate hybrid E/M states, which exist along an epithelial-mesenchymal continuum. Here, we summarize recent studies characterizing the epigenetic drivers of hybrid E/M states. We focus on the histone-modification writers, erasers, and readers that assist or oppose the canonical hybrid E/M transcription factors that modulate hybrid E/M state transitions. We also examine the role of chromatin remodelers and DNA methylation in hybrid E/M states. Finally, we highlight the challenges of targeting hybrid E/M pharmacologically, and we propose future directions that might reveal the specific and targetable mechanisms by which hybrid E/M drives metastasis in patients.

Automated summary

Epithelial-to-mesenchymal transition (EMT) is a process in cancer where cells lose their epithelial characteristics and gain mesenchymal phenotypes, driving tumor invasion and metastasis. Recent studies have identified intermediate hybrid E/M states along an epithelial-mesenchymal continuum during EMT. This summary focuses on the involvement of epigenetic regulators, chromatin remodelers, and DNA methylation in hybrid E/M states, while also addressing the challenges of pharmacologically targeting EMT and proposing future research directions.