La transition épithéliomésenchymateuse au cours du développement dans la fibrose et dans la progression tumorale

Abstract

Epithelial mesenchymal transition (EMT) is a fundamental mechanism controlling multiple events during embryonic development. Mesenchymal cells appear transiently in some diploblasts, the most primitive species characterized by two epithelial layers. Since almost 800 million years, EMT has been conserved throughout evolution to control morphogenetic events, such as the formation of the three primary germ layers during gastrulation. Most interestingly, specific molecular pathways have been conserved in many different species to drive EMT. In the animal kingdom, a recurrent theme is that EMT controls the intercellular adhesion machinery and the dynamics of its associated cytoskeleton. EMT pathways are also tightly connected to determination and differentiation programs, and are reactivated in adult tissues following injury or exposure to toxic agents. EMT is now shown to operate during the early stages of carcinoma invasion leading to blood or lymph vessel intravasation of malignant cells. The converse mechanism — mesenchymal-epithelial transition (MET) — then operates at distant sites from the primary tumor to form macrometastases from isolated micrometastatic cells. The mesenchymal-like state of carcinoma confers stemness, protection from cell death, escape from immune response and, most importantly, resistance to conventional and targeted therapies. Our laboratory has designed an EMT high-throughput screen of small molecular weight compounds and biologics in order to establish new therapeutic approaches that interfere with the plasticity of carcinoma cells. New therapeutic interventions are envisioned to delay tumor recurrence.