Epithelial-mesenchymal transition in tumor metastasis

Abstract

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.

Keywords: cancer; circulating tumor cells; epithelial-mesenchymal transition; invasion; metastasis; progression.

Figure 1

Primary epithelial tumor cells undergo epithelial–mesenchymal transition (EMT) to acquire the ability to disseminate from the original site and migrate into the surrounding stroma, and intravasate into circulation. A small number of circulating tumor cells and cell clusters survive in the vasculature and eventually extravasate into distant organs such as the lung. Disseminated tumor cells could remain in dormant state for a period of time before undergoing mesenchymal–epithelial transition (MET) to proliferate and form macrometastases.