Defining Epithelial-Mesenchymal Plasticity in Cancer Using Single-Cell Genomics

Abstract

Epithelial-mesenchymal plasticity (EMP) describes the interconversion of cells between epithelial and mesenchymal phenotypes. During the epithelial-mesenchymal transition (EMT), epithelial cells lose defining characteristics, such as stable cell-cell junctions, and gain the ability to migrate and invade through extracellular matrices. This plasticity contributes to tumour progression, promoting therapy resistance and immune cell evasion. Despite its importance, defining molecular features of this plasticity have largely remained elusive due to the limited scale of most studies. Here, I present my studies applying comparative single-cell genomics to map transcriptional changes associated with the EMT in diverse experimental conditions and EMP in tumours, I identify regulatory features associated with these dynamics, and explore opportunities to pharmacologically restrict them. This work provides critical steps towards building quantitative models of EMP, which will inform effective strategies to restrict these dynamics in cancer and improve patient prognosis.