The epithelial–mesenchymal transition under control: Global programs to regulate epithelial plasticity

The epithelial to mesenchymal transition or EMT has become one of the most exciting fields in cancer research. Nevertheless, its relevance in tumor biology and the metastatic process still faces some controversy. Clarification may arise when considering the EMT as a reversible and often incomplete process, essentially a manifestation of strong epithelial plasticity. Transient cellular states are generated to fulfill specific requirements in each and all the steps of the metastatic process, from primary tumor cell detachment to dissemination and colonization. Opposing multiple cellular programs that promote or prevent EMT, thereby destabilizing or reinforcing epithelial integrity, play a central role in the inherent cellular dynamics of cancer progression. These cell biology programs not only drive cells towards the epithelial or the mesenchymal state but also impinge into multiple cellular and global responses including proliferation, stemness, chemo and immunotherapy resistance, inflammation and immunity, all relevant for the development of the metastatic disease.