Identification, functional insights and therapeutic targeting of EMT tumour states.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a cellular process during which cells lose their epithelial characteristics and acquire mesenchymal features with enhanced migration capacities. EMT has key roles in different aspects of tumorigenesis, including tumour initiation, progression, metastasis and resistance to therapy. Here, we have reviewed the recent advances in our understanding of EMT in cancer. Instead of being a binary switch as initially proposed, EMT has been shown to be composed of multiple tumour states residing in specific niches with distinct functional properties that are controlled by different gene regulatory networks. We discuss how the types of oncogenic mutations, signalling pathways, transcription factors, epigenetic regulators and microenvironmental cues regulate the different EMT states. We also highlight the mechanisms by which EMT controls resistance to anticancer therapy and how new approaches to pharmacologically target EMT in clinical settings have recently been developed.