EMT Transition States during Tumor Progression and Metastasis

Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states. Here, we review the recent studies that demonstrate the existence of these different EMT states in cancer and the mechanisms regulating their functions. We discuss the different functional characteristics, such as proliferation, propagation, plasticity, invasion, and metastasis associated with the distinct EMT states. We summarize the role of the transcriptional and epigenetic landscapes, gene regulatory network and their surrounding niche in controlling the transition through the different EMT states. EMT occurs through distinct intermediate states in vivo. Distinct EMT transition states can be identified using cell surface markers and single-cell RNA-sequencing. Distinct EMT transition states present different functions, with the hybrid EMT state presenting the highest metastatic potential. Distinct EMT transition states present different gene expression and chromatin landscape. Distinct EMT transition states are localized in different niches that regulate cell fate transitions.