EMT or EMT-promoting transcription factors, where to focus the light?

The epithelial-to-mesenchymal transition (EMT) is commonly considered as a main driving force of the metastatic cascade. An impressive series of experiments and observations worldwide supports its pivotal role in promoting cancer cell dissemination at the invasive fronts of tumors, intravasation, cell survival in fluids, and extravasation, with secondary site colonization being the only step requiring a return to an epithelial phenotype (1). Beyond this, commitment of epithelial cells into an EMT program has been associated with resistance to chemo-, radio-, and hormono-therapies, definitively extending the interest of studying EMT from the embryologist community to the oncology and medical fields. Obviously, EMT turns out to constitute a transdifferentiation program, allowing epithelial cells to escape from numerous stresses, including mechanical constrains, hypoxia, nutrient depletion, and unfortunately therapeutic treatments (1). EMT is orchestrated by a restricted number of transcription factors mainly the three Snail, Twist, and Zeb families (EMT-TFs). With inclusion of miRNAs, these factors constitute a complex interactome, able to sensor multiple signals received from the proximal microenvironment and relay them onto gene expression (2, 3).