Abstract
Epithelial–mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and down-regulation of specific proteins, both of which are regulated by EMT-inducing transcription factors (EMT-TFs), mainly represented by the families of Snail, Twist, and ZEB proteins. This review highlights the roles of key EMT-TFs and their post-translational regulation in cancer metastasis.
Highlights
Morphological alteration in tissues is related to phenotypic changes in cells [1].Changes in morphology and functions of cells can be caused by changes in transcriptional programs and protein expression [2]
The process of epithelial–mesenchymal transition (EMT) is executed in response to these signaling factors that induce transcription factors (EMT-TFs) such as the families of Snail, Twist, and ZEB, which regulate the expression of EMT-related genes (Figure 3) [26]
Several studies have revealed that the expression of EMTinducing transcription factors (EMT-TFs) induces drug resistance in several malignant carcinomas and leads to poor prognosis for patients [42,43,44]
Summary
Morphological alteration in tissues is related to phenotypic changes in cells [1]. Changes in morphology and functions of cells can be caused by changes in transcriptional programs and protein expression [2]. The intracellular signal transduction is triggered by extracellular signal molecules binding to membrane receptors (Figure 2) Examples of such ligands are growth factors, including epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor β (TGF-β), bone morphogenetic protein, integrin, Jagged, Wnt, and Sonic Hedgehog [21,22]. The process of EMT is executed in response to these signaling factors that induce transcription factors (EMT-TFs) such as the families of Snail, Twist, and ZEB, which regulate the expression of EMT-related genes (Figure 3) [26]. Because EMT-TFs are critical factors in regulating EMT-related markers and leading to cancer metastasis, many researchers have studied the signaling pathways and PTMs of EMT-TFs. several studies have revealed that the expression of EMT-TFs induces drug resistance in several malignant carcinomas and leads to poor prognosis for patients [42,43,44]. This review will discuss the current roles and PTM-mediated regulation of EMT-TFs and the functional consequences of these PTMs in cancer metastasis
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