Epithelial-mesenchymal transition

The term "epithelial-mesenchymal transition" was initially used to describe a process of embryogenesis. The reverse process is called MET (mesenchymal-epithelial transition) . Today, the term is broader after it became clear that EMT has a decisive influence on various physiological and pathological processes, such as organ development, fibrosis and wound healing, malignant transformations, development of resistance of cytostatic drugs. EMT causes profound morphological and phenotypic changes in cells.

Epithelial and mesenchymal cells differ significantly both in their phenotype and in their functions. Epithelial, but not mesenchymal cells, are firmly connected to each other via cell contact points, e.g. tight junctions, gap junctions and adherens junctions, whereas mesenchymal cells are not.E-cadherin, which is not produced by mesenchymal cells, plays a decisive role in this process. Mesenchymal cells express N-cadherin, fibronectin and vimentin.

During re-epithelialisation of a wound, when keratinocytes at the wound edges spread over the non-epithelialised area, EMT plays an important role.

EMT also plays a decisive role in the implantation of an embryo. The trophoectodermal cells use the process of EMT to invade the endometrium.

In the process of metastasis of epithelial tumors, the MET-induced invasion of cells is a crucial step. Carcinoma cells lose "cell-cell adhesion", depending on the carcinoma progression of the primary tumor. This process is initiated by the suppression of E-cadherin. TGF-beta can initiate this process when it encounters RAS-expressing epithelial cells. In this process TGF-beta also suppresses apoptosis. The tumor cells are then able to break through the basement membrane and enter the blood stream (intravasation). This effect is reversible by inducers of epithelial differentiation like GATA3. At a later stage, when circulating carcinoma cells leave the blood stream to form micrometastases, they use the opposite process to EMT, a "mesenchymal-epithelial transition", MET for short.

Recent studies have shown the role of EMT in the development of resistance of tumor cells to chemotherapeutic agents.

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