The epithelial-to-mesenchymal transition in cancer: pathogenetic features

Abstract

The epithelial‑to‑mesenchymal transition (EMT) is a cellular biological process, that occurs in a wide range of cells and tissues and is triggered by complex regulatory networks involving transcriptional control with SNAIL, ZEB1, ZEB2, Twist, SLUG, E‑cadherin, vimentin, tumor microenvironment and genetic characteristics. EMT is represented by the multi‑stage development and transformation of cells of the epithelial phenotype into cells that acquire mesenchymal features of various severity. These quasi‑mesenchymal cells are characterized by stemness, tumor heterogeneity, increasing invasiveness, drug resistance and a tendency to distant metastasis, which leads to the proliferation of neoplastic cells, tumor dissemination and initiation of metastasis, which induces the therapy resistance and the oncological recurrence.This review is based on the latest scientific publications about the EMT phenomenon, indexed in PubMed. The aim of the study was to evaluate the biochemical and molecular pathogenetic mechanisms of EMT and the effect of EMT markers on the progression of neoplastic processes and the effectiveness of the treatment. Nowadays the proper EMT scheme that combines all the molecular transformations of sells with quasi‑mesenchymal phenotype doesn’t exist. But analyzing the features of this cellular program, we can find the proper therapy, that could be able to suppress the plasticity of cancer cells, prevent EMT induction by blocking contextual signals, and induce mesenchymal‑epithelial transition. All these aspects will lead to the reduction of the risk of tumor dissemination and the increase of the effectiveness of cancer treatment.

Keywords

• epithelial‑to‑mesenchymal transition
• tumor microenvironment
• stemness
• tumor heterogeneity
• cancer stem cell