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      Guidelines and definitions for research on epithelial–mesenchymal transition

      review-article
      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 47 , 34 , 35 , 36 , 5 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , , On behalf of the EMT International Association (TEMTIA)
      Nature Reviews. Molecular Cell Biology
      Nature Publishing Group UK
      Cancer, Developmental biology, Epithelial-mesenchymal transition

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          Abstract

          Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.

          Abstract

          In this Consensus Statement, the authors (on behalf of the EMT International Association) propose guidelines to define epithelial–mesenchymal transition, its phenotypic plasticity and the associated multiple intermediate epithelial–mesenchymal cell states. Clarification of nomenclature and definitions will help reduce misinterpretation of research data generated in different experimental model systems and promote cross-disciplinary collaboration.

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          Most cited references96

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          New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

          Epithelial-mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell-cell and cell-extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas.
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            EMT: 2016.

            The significant parallels between cell plasticity during embryonic development and carcinoma progression have helped us understand the importance of the epithelial-mesenchymal transition (EMT) in human disease. Our expanding knowledge of EMT has led to a clarification of the EMT program as a set of multiple and dynamic transitional states between the epithelial and mesenchymal phenotypes, as opposed to a process involving a single binary decision. EMT and its intermediate states have recently been identified as crucial drivers of organ fibrosis and tumor progression, although there is some need for caution when interpreting its contribution to metastatic colonization. Here, we discuss the current state-of-the-art and latest findings regarding the concept of cellular plasticity and heterogeneity in EMT. We raise some of the questions pending and identify the challenges faced in this fast-moving field.
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              Emerging Biological Principles of Metastasis.

              Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge.
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                Author and article information

                Contributors
                jingyang@ucsd.edu
                sheng@kumamoto-u.ac.jp
                Journal
                Nat Rev Mol Cell Biol
                Nat. Rev. Mol. Cell Biol
                Nature Reviews. Molecular Cell Biology
                Nature Publishing Group UK (London )
                1471-0072
                1471-0080
                16 April 2020
                16 April 2020
                2020
                : 21
                : 6
                : 341-352
                Affiliations
                [1 ]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Departments of Pharmacology and Pediatrics, Moores Cancer Center, , University of California, San Diego, ; La Jolla, CA USA
                [2 ]ISNI 0000 0001 2168 186X, GRID grid.134563.6, Department of Cellular and Molecular Medicine, , University of Arizona, ; Tucson, AZ USA
                [3 ]ISNI 0000 0001 2069 7798, GRID grid.5342.0, Molecular and Cellular Oncology Lab, Department of Biomedical Molecular Biology, , Ghent University, Cancer Research Institute Ghent (CRIG), VIB Center for Inflammation Research, ; Ghent, Belgium
                [4 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Laboratory of Stem Cells and Cancer, , Université Libre de Bruxelles, ; Bruxelles, Belgium
                [5 ]ISNI 0000 0001 2107 3311, GRID grid.5330.5, Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, , Friedrich-Alexander-University Erlangen-Nürnberg, ; Erlangen, Germany
                [6 ]ISNI 0000000107068890, GRID grid.20861.3d, Division of Biology and Biological Engineering, , California Institute of Technology, ; Pasadena, CA USA
                [7 ]ISNI 0000 0004 1936 9262, GRID grid.11835.3e, Department of Biomedical Science and Bateson Centre, , University of Sheffield, ; Sheffield, UK
                [8 ]ISNI 0000000119578126, GRID grid.5515.4, Departamento de Bioquímica, , Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPAZ & Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), ; Madrid, Spain
                [9 ]ISNI 0000 0004 1757 9848, GRID grid.428973.3, Institute for Research in Biomedicine (IRB Barcelona), , Barcelona Institute of Science and Technology/Institut de Biologia Molecular de Barcelona (IBMB-CSIC), ; Barcelona, Spain
                [10 ]ISNI 0000 0004 1937 0642, GRID grid.6612.3, Department of Biomedicine, , University of Basel, ; Basel, Switzerland
                [11 ]ISNI 0000 0001 0702 3000, GRID grid.248762.d, Department of Biochemistry and Molecular Biology, , University of British Columbia and British Columbia Cancer Research Centre, ; Vancouver, BC Canada
                [12 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Departments of Cell and Tissue Biology, and Anatomy, , University of California at San Francisco, ; San Francisco, CA USA
                [13 ]ISNI 0000 0001 0703 675X, GRID grid.430503.1, Department of Pharmacology, , University of Colorado Anschutz Medical Campus, ; Aurora, CO USA
                [14 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Laboratory Medicine (LABMED), Division of Pathology, , Karolinska University Hospital and Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, ; Stockholm, Sweden
                [15 ]ISNI 0000 0001 2172 2676, GRID grid.5612.0, Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) and Departament de Ciències Experimentals i de la Salut, , Universitat Pompeu Fabra, ; Barcelona, Spain
                [16 ]ISNI 0000 0000 8994 5086, GRID grid.1026.5, Centre for Cancer Biology, , An alliance of SA Pathology and University of South Australia, ; Adelaide, SA Australia
                [17 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Developmental Biology Program, Sloan Kettering Institute, , Memorial Sloan Kettering Cancer Center, ; New York, NY USA
                [18 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, School of Medicine, College of Medicine, , National Taiwan University, ; Taipei, Taiwan
                [19 ]ISNI 0000 0004 1937 0538, GRID grid.9619.7, Department of Medical Neurobiology, Institute for medical Research Israel-Canada and the Safra Center for Neurosciences, , Hebrew University of Jerusalem, Hadassah Medical School, ; Jerusalem, Israel
                [20 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Cancer Biology, , Metastasis Research Center, MD Anderson Cancer Center, ; Houston, TX USA
                [21 ]ISNI 0000 0001 2097 5006, GRID grid.16750.35, Department of Molecular Biology, , Princeton University, ; Princeton, NJ USA
                [22 ]ISNI 0000 0000 8994 5086, GRID grid.1026.5, Centre for Cancer Biology, , an Alliance of SA Pathology and the University of South Australia, ; Adelaide, SA Australia
                [23 ]ISNI 0000 0001 2173 3359, GRID grid.261112.7, Department of Physics, , Northeastern University, ; Boston, MA USA
                [24 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Anatomic Pathology, The Division of Pathology and Laboratory Medicine, , University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [25 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Medicine (Oncology) and Department of Cell Biology and Physiology, , ICCE Institute, Washington University, ; St. Louis, MO USA
                [26 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Translational Molecular Pathology, , University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [27 ]ISNI 0000 0001 2171 9952, GRID grid.51462.34, Cancer Biology and Genetics Program, Sloan Kettering Institute, , Memorial Sloan Kettering Cancer Center, ; New York, NY USA
                [28 ]ISNI 0000000121901201, GRID grid.83440.3b, Department of Cell and Developmental Biology, , University College London, ; London, UK
                [29 ]ISNI 0000 0004 1936 7961, GRID grid.26009.3d, Department of Biology, , Duke University, ; Durham, NC USA
                [30 ]ISNI 0000 0001 2297 6811, GRID grid.266102.1, Departments of Anatomy and Biochemistry/Biophysics, , University of California, San Francisco, School of Medicine, ; San Francisco, CA USA
                [31 ]Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC Australia
                [32 ]ISNI 0000 0004 1759 6875, GRID grid.466805.9, Instituto de Neurociencias (CSIC-UMH) Avda Ramon y Cajal s/n, ; Sant Joan d´Alacant, Spain
                [33 ]ISNI 0000 0004 0384 0005, GRID grid.462282.8, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, ; Lyon, France
                [34 ]ISNI 0000 0001 2168 186X, GRID grid.134563.6, Department of Cellular and Molecular Medicine, , University of Arizona, ; Tucson, AZ USA
                [35 ]ISNI 0000 0004 4910 6535, GRID grid.460789.4, INSERM UMR 1186, Integrative Tumor Immunology and Genetic Oncology, Gustave Roussy, , University Paris-Saclay, ; Villejuif, France
                [36 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Department of Medicine, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [37 ]ISNI 0000 0004 0372 2033, GRID grid.258799.8, Department of Zoology, Graduate School of Science, , Kyoto University, ; Kyoto, Japan
                [38 ]RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
                [39 ]ISNI 0000 0001 2353 1689, GRID grid.11417.32, Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, ; Toulouse, France
                [40 ]Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Guangzhou, China
                [41 ]ISNI 0000000406180938, GRID grid.489335.0, School of Biomedical Sciences and Institute of Health and Biomedical Innovation, , Queensland University of Technology, Translational Research Institute, ; Woolloongabba, QLD Australia
                [42 ]ISNI 0000 0001 2341 2786, GRID grid.116068.8, Whitehead Institute for Biomedical Research, Department of Biology, , MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, ; Cambridge, MA USA
                [43 ]ISNI 0000000089150953, GRID grid.1024.7, Australian Prostate Cancer Research Centre-Queensland (APCRC-Q) and Queensland Bladder Cancer Initiative (QBCI), School of Biomedical Sciences and Institute of Health and Biomedical Innovation, , Queensland University of Technology, ; Woolloongabba, QLD Australia
                [44 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Computational and Systems Biology and UPMC-Hillman Cancer Center, , University of Pittsburgh, ; Pittsburgh, PA USA
                [45 ]ISNI 0000 0004 1936 8438, GRID grid.266539.d, Department of Molecular and Cellular Biochemistry and UK Markey Cancer Center, , University of Kentucky College of Medicine, ; Lexington, KY USA
                [46 ]ISNI 0000 0001 0660 6749, GRID grid.274841.c, International Research Center for Medical Sciences (IRCMS), , Kumamoto University, ; Kumamoto, Japan
                [47 ]ISNI 0000 0004 0639 6384, GRID grid.418596.7, Present Address: Institut Curie, PSL Research University, ; Paris, France
                Author information
                http://orcid.org/0000-0001-8410-3549
                http://orcid.org/0000-0003-4576-9377
                http://orcid.org/0000-0002-1626-6730
                http://orcid.org/0000-0001-9053-9613
                http://orcid.org/0000-0002-8123-6247
                http://orcid.org/0000-0002-3467-6389
                http://orcid.org/0000-0002-3538-840X
                http://orcid.org/0000-0002-9938-3798
                http://orcid.org/0000-0002-7410-916X
                http://orcid.org/0000-0002-7866-3686
                http://orcid.org/0000-0002-9931-3378
                http://orcid.org/0000-0001-6510-5717
                http://orcid.org/0000-0003-0478-5020
                http://orcid.org/0000-0002-9723-4924
                http://orcid.org/0000-0002-3364-6655
                http://orcid.org/0000-0002-3700-8765
                Article
                237
                10.1038/s41580-020-0237-9
                7250738
                32300252
                76a02086-3f2e-4e68-96d3-ea2e2fff1be8
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 March 2020
                Categories
                Consensus Statement
                Custom metadata
                © Springer Nature Limited 2020

                cancer,developmental biology,epithelial-mesenchymal transition

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