The capacity of cells to modify their phenotypes from epithelial to mesenchymal (epithelial-to-mesenchymal transition or EMT) and vice versa provides them with a dynamic plasticity essential for human life, from embryogenesis to wound healing. Current knowledge about carcinogenetic mechanisms leaves little doubts on the pivotal participation of these interchangeable processes in cancer development, and their influence has been quite clearly established in the progression of cutaneous squamous cell carcinoma. A complex and ordered interplay of signals induces the shift between both phenotypes, providing cells with the most suitable state at every moment to face the next step in tumor invasion and dissemination. Some stimulatory triggers have opposite effects according to the biological context and in many cases exert collateral functions. This scenario makes finding an ideal therapeutic target difficult but provides the opportunity to intervene simultaneously at many different levels with small actions such as targeting the tumor environment. In any case, advances in knowledge of the EMT mechanisms and their influence on carcinogenesis and drug resistance will greatly influence the therapeutic strategies for many human tumors, including cutaneous squamous cell carcinoma.
Keywords: Epithelial-to-mesenchymal; Skin; Squamous cell carcinoma; YAP; microRNA; p63.