Body processes

Epithelial-mesenchymal transition – function, role & diseases

Epithelial-mesenchymal transition

The epithelial-mesenchymal transition , also called EMT , describes the transformation of epithelial cells into mesenchymal cells . This transformation is of great importance for embryonic development . However, this process also plays a key role in the formation of metastases in carcinomas.

What is the epithelial-mesenchymal transition

An epithelial-mesenchymal transition is a transformation of already differentiated epithelial cells into undifferentiated mesenchymal stem cells . This process is particularly important during embryonic development.

As part of this transformation, the epithelial cells are released from their bond and can migrate in the body. They pass through the basement membrane. The basement membrane separates the epithelium , the glial cells and the endothelium from the connective tissue-like intercellular space. As undifferentiated multipotent stem cells, the migrated cells reach all areas of the developing organism and can be differentiated again into any cell type.

The epithelial cells form the so-called epithelium, which is a collective term for the glandular and cover tissue. The mesenchyme comprises the gelatinous and embryonic connective tissue from which bone , cartilage , smooth muscle , cardiac muscle , kidneys , adrenal cortex , the hematopoietic system with blood and lymphatic vessels , and reticular, tight and loose connective tissue develop.

function & task

The epithelial-mesenchymal transition is an important process during embryogenesis. During this time there is increased growth, in which all the cells in the body participate. Epithelial cells that have already differentiated are also included in these growth processes. To do this, however, they have to be converted back into multipotent stem cells.

The most intensive growth takes place in the first eight weeks of pregnancy . The actual process of embryogenesis begins around the sixth day of pregnancy after the so-called germ stage (cell development) and lasts until the end of the eighth week of pregnancy. In this phase, the epithelial-mesenchymal transition is of great importance, since all organs are now being created. Many epithelial cells lose their differentiation and binding here again. They migrate through the basement membrane and are distributed throughout the body. There they again behave like normal multipotent stem cells and undergo renewed differentiation into different cell types.

Of course, they can also differentiate back into epithelial cells. To do this, the cell contacts must first be reduced and the polarity of the epithelial cells reversed. Cell contact is understood to mean the cohesion of the cells by so-called adhesion molecules. An important adhesion molecule is, inter alia, E-cadherin. E-cadherin is a transmembrane glycoprotein that is calcium ion dependent. It connects epithelial cells to each other and ensures cell polarity and signal transmission. During embryogenesis, the activity of E-cadherin is reduced. This leads to the dissolution of the cell structure. At the same time, the polarity of the cells also disappears.

The epithelial cells have both a so-called apical (outer) side and a basal side, which faces the underlying tissue. The outer side is on the surface of the skin and mucous membranes , while the basal side is connected to connective tissue located under a basal lamina. Both sides have different functional and structural differences, thus providing the morphology of the organs. However, embryogenesis requires rapid changes and flexibility of the cells to be able to quickly adapt to the growth processes.

After the end of embryogenesis, the epithelial-mesenchymal transition loses its importance for the organism.

Diseases & Ailments

The epithelial-mesenchymal transition (EMT) only benefits the organism during the very short period of embryogenesis. After the turbulent growth phase, the cells are fully differentiated. The need for a large number of multipotent stem cells then no longer exists. Therefore, this process is disabled.

If, despite this, the epithelial-mesenchymal transition is activated after embryogenesis has ended, this usually occurs in connection with malignant tumor diseases. EMT is responsible for the development of metastases in the context of cancer . The process is similar to embryogenesis. Overall, it is a complex process based on genetic regulatory mechanisms that are not yet fully understood. So are many responsible genesonly active during embryonic development. After that they will be decommissioned. A possible reason for the renewed activation of these genes could be the upregulation of the transcription factor Sox4. Corresponding research results were presented at the University of Basel. In turn, Sox4 activates a number of other genes involved in epithelial-mesenchymal transition.

The inactivity of the corresponding genes is said to be due to their illegibility due to being coated with certain proteins ( histones ). However, the Sox4 gene ensures the production of an enzyme called Ezh2. It is a methyltransferase that causes the methylation of the corresponding histones. The other genes involved become readable again and thus activate the epithelial-mesenchymal transition.

The change in the genetic material takes place within a cancerous tumor and thus provides the cause for the complete de-differentiation of the cancer cells. Without an epithelial-mesenchymal transition, the cancer would only grow at the site of its origin and would not spread. Metastasis, however, makes a tumor particularly malignant and aggressive. Therefore, work is being done on the development of drugs that inhibit the formation of the methyltransferase Ezh2. Appropriate drugs have already been developed, but they are still being tested. Containing the formation of metastases would, on the one hand, reduce the aggressiveness of cancer growth and, on the other hand, open up the opportunity to treat previously hopeless cases curatively.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.