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      The relationship between vasculogenic mimicry and epithelial‐mesenchymal transitions

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          Abstract

          Vasculogenic mimicry ( VM) is a vascular‐like structure which can mimic the embryonic vascular network pattern to nourish the tumour tissue. As a unique perfusion way, VM is correlated with tumour progression, invasion, metastasis and lower 5‐year survival rate. Notably, epithelial‐mesenchymal transition ( EMT) regulators and EMT‐related transcription factors are highly up‐regulated in VM‐forming tumour cells, which demonstrated that EMT may play a crucial role in VM formation. Therefore, the up‐regulation of EMT‐associated adhesion molecules and other factors can also make a contribution in VM‐forming process. Depending on these discoveries, VM and EMT can be utilized as therapeutic target strategies for anticancer therapy. The purpose of this article is to explore the advance research in the relationship of EMT and VM and their corresponding mechanisms in tumorigenesis effect.

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          Most cited references59

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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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            A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.

            Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.
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              Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.

              The epithelial-mesenchymal transition (EMT), one of the main mechanisms underlying development of cancer metastasis, induces stem-like properties in epithelial cells. Bmi1 is a polycomb-group protein that maintains self-renewal, and is frequently overexpressed in human cancers. Here, we show the direct regulation of BMI1 by the EMT regulator, Twist1. Furthermore, Twist1 and Bmi1 were mutually essential to promote EMT and tumour-initiating capability. Twist1 and Bmi1 act cooperatively to repress expression of both E-cadherin and p16INK4a. In patients with head and neck cancers, increased levels of both Twist1 and Bmi1 correlated with downregulation of E-cadherin and p16INK4a, and was associated with the worst prognosis. These results suggest that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes.
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                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                29 March 2016
                September 2016
                : 20
                : 9 ( doiID: 10.1111/jcmm.2016.20.issue-9 )
                : 1761-1769
                Affiliations
                [ 1 ] Department of OncologyShandong University School of Medicine Jinan Shandong ProChina
                [ 2 ] Department of Radiation OncologyQianfoshan Hospital Affiliated to Shandong University Jinan Shandong ProChina
                [ 3 ] Department of OncologyWeifang Medical College Weifang Shandong ProChina
                Author notes
                [*] [* ] Correspondence to: Jiandong ZHANG, M.D., Ph.D.

                E‐mail: zhangjd165@ 123456sina.com

                Article
                JCMM12851
                10.1111/jcmm.12851
                4988285
                27027258
                5cbb2ed0-8e8e-432d-9a63-cdff2e9160fb
                © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 January 2016
                : 24 February 2016
                Page count
                Pages: 9
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                jcmm12851
                September 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:17.08.2016

                Molecular medicine
                vasculogenic mimicry,epithelial‐mesenchymal transition,cancer,antitumour,tumorigenesis

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