Epithelial-mesenchymal transition (EMT) is critical for appropriate embryonic development, and this process is re-engaged in adults during wound healing, tissue regeneration, organ fibrosis, and cancer progression. Inflammation is a crucial conspirator in the emergence of EMT in adults but is absent during embryonic development. As highlighted in this Review series, EMT is now a recognized mechanism for dispersing cells in embryos, forming fibroblasts/mesenchymal cells in injured tissues, and initiating metastasis of epithelial cancer cells. Also discussed are proposals to classify EMT into three subtypes, each of which has different functional consequences.
The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
Raghu Kalluri, Robert A. Weinberg
Somatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon — namely, the transition of epithelial and endothelial cells to a motile phenotype.
Michael Zeisberg, Eric G. Neilson
The events that convert adherent epithelial cells into individual migratory cells that can invade the extracellular matrix are known collectively as epithelial-mesenchymal transition (EMT). Throughout evolution, the capacity of cells to switch between these two cellular states has been fundamental in the generation of complex body patterns. Here, we review the EMT events that build the embryo and further discuss two prototypical processes governed by EMT in amniotes: gastrulation and neural crest formation. Cells undergo EMT to migrate and colonize distant territories. Not surprisingly, this is also the mechanism used by cancer cells to disperse throughout the body.
Hervé Acloque, Meghan S. Adams, Katherine Fishwick, Marianne Bronner-Fraser, M. Angela Nieto