Cancer is the second leading cause of death in the world, and metastasis is the major cause of cancer-related death. Metastasis is a dynamic and complex process in which a subset of cancer cells dissociates from the primary tumor, gains migratory potential, and colonizes specific distant organs. The dynamic and multi-step nature of metastasis still remains the least understood aspect of cancer biology. The epithelial-to-mesenchymal (EMT) transition processes are normally observed during embryonic development and are active in some pathological stages including cancer metastasis. During the EMT process, cancer cells lose their cell-cell contacts and acquire migratory properties. Furthermore, EMT-programme activation is a critical regulator of cancer stem cell (CSC) phenotypes and confers cells’ resistance to drug therapy. Conversely, for the successful development of metastasis in distant organs, cancer cells must revert to their original phenotype by re-expressing epithelial proteins and losing mesenchymal features (i.e., mesenchymal-to-epithelial transition, MET). During embryonic development, cells display epithelial-mesenchymal plasticity (EMP), with a dynamic flux between EMT and MET markers. Recent studies showed that EMP features could be observed in silico, in vitro, and in vivo experiments, in multiple subtypes of cancer cell lines, and primary tumors. This EMP model can contribute to the understanding of metastasis biology, and facilitate the development of therapeutics to target metastatic cells.
