THE ROLE AND MECHANISMS OF EPITHELIAL-MESENCHYMAL TRANSITION IN THE PROGRESSION OF MELANOMA

Abstract

Despite the achievements of modern medicine in the diagnosis and treatment of oncological diseases, skin melanoma remains one of the leading causes of death worldwide: every third case of melanoma ends in death. As you know, one of the main causes of death is the high incidence of melanoma progression. It is important to note that the mechanisms of melanoma progression are diverse and the rapidly developing area of drug therapy for tumors requires a deep understanding of their characteristics. This is primarily due to the fact that these processes lead to the formation of special, minor tumor clones with stem properties. They are highly resistant to therapy. The latter is the mainobstacle to effective treatment of melanoma patients. The epithelial-mesenchymal transition (EMT) plays a leading role in the acquisition of metastatic potential by melanoma cells. An important distinguishing feature of EMT is a change in the level of expression of transmembrane glycoproteins involved in cell adhesion. With EMT, both a decrease in the level of E-cadherin and an increase in the expression of N-cadherin are observed. Such a switch in different classes of adhesion molecules leads to the fact that melanoma cells lose contact with neighboring keratinocytes and begin to interact with fibroblasts and endothelial cells. The key regulator in EMT induction in melanoma is the Notch1 signaling pathway, which accelerates N-cadherin expression when activated. In addition, EMT also regulates many other pathways – RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, the dysregulation of which is associated with the development of drug resistance in melanoma. The analysis was carried out in the article of modern literature data on the importance of EMT in carcinogenesis and prognosis of melanoma. The modern mechanisms of EMT, currently known prognostic factors, as well as potential therapeutic targets that affect EMT and, accordingly, inhibit the process of metastasis, are described in detail.