Epithelial-mesenchymal transition

doi:10.1242/jcs.02552 The epithelial-mesenchymal transition (EMT) is an orchestrated series of events in which cell-cell and cell-extracellular matrix (ECM) interactions are altered to release epithelial cells from the surrounding tissue, the cytoskeleton is reorganized to confer the ability to move through a three-dimensional ECM, and a new transcriptional program is induced to maintain the mesenchymal phenotype. Essential for embryonic development, EMT is nevertheless potentially destructive if deregulated, and it is becoming increasingly clear that inappropriate utilization of EMT mechanisms is an integral component of the progression of many tumors of epithelial tissues. Structural integrity is a key property of epithelial tissues: external epithelia serve as protective barriers against environmental hazards, and internal epithelia create defined and physiologically controlled subdomains within the organism. Epithelial structure is maintained by cell-cell interactions. These involve tight junctions, cadherin-based adherens junctions that are connected to the actin cytoskeleton, gap junctions that allow direct chemical interactions between neighboring cells, and desmosomes connected to the intermediate filament cytoskeleton, and cell-ECM interactions mediated by integrins and other molecules. The cell-cell and cell-ECM contacts also define tissue polarity (Yeaman et al., 1999), which allows different functions for the apical and basal surfaces. By contrast, many mesenchymal cells exist largely without direct cell-cell contacts and defined cell polarity, and have distinct cell-ECM interactions and cytoskeletal structures. Mesenchymal cells can contribute to the ECM by synthesizing and organizing new components and by remodeling the ECM through the production of matrix-degrading metalloproteinases (MMPs). Mesenchymal cells are also abundant sources of signaling proteins that act on epithelial cells, including growth factors of the epidermal (EGF), heptocyt