Epithelial–mesenchymal transition in tumor metastasis

The epithelial–mesenchymal transition (EMT) is a developmental program that enables stationary epithelial cells to gain the ability to migrate and invade as single cells. Tumor cells reactivate EMT to acquire molecular alterations that enable the partial loss of epithelial features and partial gain of a mesenchymal phenotype. Our understanding of the contribution of EMT to tumor invasion, migration, and metastatic outgrowth has evolved over the past decade. In this review, we provide a summary of both historic and recent studies on the role of EMT in the metastatic cascade from various experimental systems, including cancer cell lines, genetic mouse tumor models, and clinical human breast cancer tissues. The epithelial–mesenchymal transition (EMT) enables primary epithelial tumor cells to acquire the ability to migrate and disseminate into the surrounding stroma and vasculature. A small proportion of circulating tumor cells and cell clusters eventually extravasate into distant organs. The reverse process, the mesenchymal–epithelial transition, allows proliferation and formation of macrometastases. The accompanying model summarizes our current understanding of the role of EMT in the metastatic cascade.