Tumor Microenvironment: Involved Factors and Signaling Pathways in Epithelial-Mesenchymal Transition

Abstract

Context: Metastasis is a main cause of death in patients with cancer, whereby tumor cells withdraw from the primary site of the tumor mass and produce secondary tumor mass in new sites. Primary tumor cells depart collectively and individually to invade closed and distant sites. Evidence Acquisition: This review considers TME-derived factors that actuate signaling pathways to induce epithelial-mesenchymal transition (EMT). National Center for Biotechnology Information (NCBI) was the main resource. Google Scholar and Scopus were other databases for finding articles. Keywords that were inserted into the search box of databases to identify related articles were ‘metastasis’, ‘invasion’, ‘epithelial-mesenchymal transition’, ‘EMT’, ‘tumor microenvironment’, ‘TME’, ‘TME cells’, and ‘signaling pathway in EMT’. Titles and abstracts of the articles were studied to choose the right articles. Finally, 100 articles were selected to study in detail and use as references. Results: EMT is a type of metastasis that deprives epithelial single-cells of their characteristic features and acquires mesenchymal features facilitating the departure from the primary tumor mass. During EMT, cell-adhesion and apical-basal polarity rapture and cells obtain movement capability. The tumor microenvironment (TME) leads EMT through secretion factors and signaling pathways. As a result of activating these pathways, transcription factors that abolish epithelial gene expressions and augment mesenchymal gene expression are induced. Conclusions: In this review, recent research published in TME and EMT fields were highlighted and critically appraised. Effect of factors-derived TME cells on EMT were manifested that propose favorite targets for a therapeutic goal to inhibit metastasis. However, data about the effect of the combination of TME cells on metastasis have a small part in the literature.

Aspects of the Epigenetic Regulation of EMT Related to Cancer Metastasis

“…Expression of E-cadherin, β-catenin, and γ-catenin is masked by TWIST1, but the expression of vimentin is increasing. Importantly, even a strong EMT-inducing transcription factor operates differentially in each cell type belonging to a different EMT status [ 48 , 49 ].…”

“…Expression of E-cadherin, β-catenin, and γ-catenin is masked by TWIST1, but the expression of vimentin is increasing. Importantly, even a strong EMT-inducing transcription factor operates differentially in each cell type belonging to a different EMT status [48,49]. SNAI1 (Snail family transcriptional repressor 1) is the member of the SNAIL family that is the best studied EMT transcription factor and is predominantly expressed in cell lines with an epithelial phenotype.…”

Sodium Butyrate as Histone Deacetylase Inhibitor Can Alter miR-101, ZEB1, ZEB2, and E-cadherin Expression in MDA-MB-468 Cells as Triple Negative Breast Cancer Cells

“…In recent literature, TNBC has been proposed as the most aggressive group of breast cancer. Cell invasion is involved in the progression of breast cancer cell metastasis, and EMT-associated factors are a prominent feature of TNBC (5,6,19).…”

“…Meta stasis is a multi-stage process and is one of the most feared aspects of cancer mortality. In the first two stages, tumor cells detach from the basement membrane and extracellular matrix (5,6). Recent studies have shown that metastasis is closely related to the process of epithelia-mesenchymal transition (EMT) (7).…”

Cerebral Glioblastoma: A Review on Genetic Alterations, Signaling Pathways, and Clinical Managements

“…The tyrosine kinase epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that stimulates cell survival, mobility, growth, and proliferation (3,(11)(12)(13). This receptor is made of a single polypeptide chain with three domains (Figure 1) (14); the extracellular domain has five regions, including the ligand-binding site (14), the intracellular domain consisting of the regulatory region, tyrosine kinase, juxtamembrane, and lastly the transmembrane domain (14).…”