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      Epithelial–mesenchymal transition and its transcription factors

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          Abstract

          Epithelial–mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors (TFs) including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT TFs and discussed their role in the process. We have also tried to focus on their mechanism of action, their interdependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type-dependent manner.

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Molecular mechanisms of epithelial-mesenchymal transition.

            The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.
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              The basics of epithelial-mesenchymal transition.

              The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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                Author and article information

                Contributors
                Journal
                Biosci Rep
                Biosci Rep
                bsr
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                28 January 2022
                23 December 2021
                : 42
                : 1
                : BSR20211754
                Affiliations
                Amity Institute of Biotechnology, Amity University Kolkata, West Bengal, India
                Author notes
                Correspondence: Santanu Palchaudhuri ( spalchaudhuri@ 123456kol.amity.edu )
                [*]

                These authors contributed equally to this work.

                [†]

                Present address: Tata Medical Centre, Kolkata, West Bengal, India

                Author information
                https://orcid.org/0000-0003-1220-8135
                Article
                BSR20211754
                10.1042/BSR20211754
                8703024
                34708244
                f0a032f0-92c8-453a-a399-f3ca8293bd74
                © 2021 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 24 July 2021
                : 26 October 2021
                : 28 October 2021
                : 16 November 2021
                Page count
                Pages: 29
                Categories
                Cancer
                Cell Migration, Adhesion & Morphology
                Developmental Biology
                Gene Expression & Regulation
                Molecular Bases of Health & Disease
                Review Articles

                Life sciences
                epithelial mesenchymal transition,gene expression regulation,transcription factor,transcriptional regulatory network

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