Guidelines and definitions for research on epithelial-mesenchymal transition

Jing Yang¹, Parker Antin², Geert Berx³, Cédric Blanpain⁴, Thomas Brabletz⁵, Marianne Bronner⁶, Kyra Campbell⁷, Amparo Cano⁸, Jordi Casanova⁹, Gerhard Christofori¹⁰, Shoukat Dedhar¹¹, Rik Derynck¹², Heide L Ford¹³, Jonas Fuxe¹⁴, Antonio García de Herreros¹⁵, Gregory J Goodall¹⁶, Anna-Katerina Hadjantonakis¹⁷, Ruby Y J Huang¹⁸, Chaya Kalcheim¹⁹, Raghu Kalluri²⁰, Yibin Kang²¹, Yeesim Khew-Goodall²², Herbert Levine²³, Jinsong Liu²⁴, Gregory D Longmore²⁵, Sendurai A Mani²⁶, Joan Massagué²⁷, Roberto Mayor²⁸, David McClay²⁹, Keith E Mostov³⁰, Donald F Newgreen³¹, M Angela Nieto³², Alain Puisieux^{33

34}, Raymond Runyan², Pierre Savagner³⁵, Ben Stanger³⁶, Marc P Stemmler⁵, Yoshiko Takahashi³⁷, Masatoshi Takeichi³⁸, Eric Theveneau³⁹, Jean Paul Thiery⁴⁰, Erik W Thompson⁴¹, Robert A Weinberg⁴², Elizabeth D Williams⁴³, Jianhua Xing⁴⁴, Binhua P Zhou⁴⁵, Guojun Sheng⁴⁶; EMT International Association (TEMTIA)

Affiliations

¹ Departments of Pharmacology and Pediatrics, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. [email protected].
² Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
³ 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 Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Bruxelles, Belgium.
⁵ Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
⁶ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁷ Department of Biomedical Science and Bateson Centre, University of Sheffield, Sheffield, UK.
⁸ 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 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology/Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Barcelona, Spain.
¹⁰ Department of Biomedicine, University of Basel, Basel, Switzerland.
¹¹ Department of Biochemistry and Molecular Biology, University of British Columbia and British Columbia Cancer Research Centre, Vancouver, BC, Canada.
¹² Departments of Cell and Tissue Biology, and Anatomy, University of California at San Francisco, San Francisco, CA, USA.
¹³ Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹⁴ 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 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 Centre for Cancer Biology, An alliance of SA Pathology and University of South Australia, Adelaide, SA, Australia.
¹⁷ Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸ School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁹ 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 Department of Cancer Biology, Metastasis Research Center, MD Anderson Cancer Center, Houston, TX, USA.
²¹ Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
²² Centre for Cancer Biology, an Alliance of SA Pathology and the University of South Australia, Adelaide, SA, Australia.
²³ Department of Physics, Northeastern University, Boston, MA, USA.
²⁴ Department of Anatomic Pathology, The Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁵ Department of Medicine (Oncology) and Department of Cell Biology and Physiology, ICCE Institute, Washington University, St. Louis, MO, USA.
²⁶ Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁷ Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁸ Department of Cell and Developmental Biology, University College London, London, UK.
²⁹ Department of Biology, Duke University, Durham, NC, USA.
³⁰ 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 Instituto de Neurociencias (CSIC-UMH) Avda Ramon y Cajal s/n, Sant Joan d´Alacant, Spain.
³³ Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.
³⁴ Institut Curie, PSL Research University, Paris, France.
³⁵ INSERM UMR 1186, Integrative Tumor Immunology and Genetic Oncology, Gustave Roussy, University Paris-Saclay, Villejuif, France.
³⁶ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³⁷ Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
³⁸ RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
³⁹ 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 School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolloongabba, QLD, Australia.
⁴² Whitehead Institute for Biomedical Research, Department of Biology, MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴³ 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 Department of Computational and Systems Biology and UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
⁴⁵ Department of Molecular and Cellular Biochemistry and UK Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.
⁴⁶ International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. [email protected].

PMID: 32300252
PMCID: PMC7250738
DOI: 10.1038/s41580-020-0237-9

Review

Guidelines and definitions for research on epithelial-mesenchymal transition

Jing Yang et al. Nat Rev Mol Cell Biol. 2020 Jun.

. 2020 Jun;21(6):341-352.

doi: 10.1038/s41580-020-0237-9. Epub 2020 Apr 16.

Authors

Affiliations

¹ Departments of Pharmacology and Pediatrics, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. [email protected].
² Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
³ 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 Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles, Bruxelles, Belgium.
⁵ Department of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
⁶ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁷ Department of Biomedical Science and Bateson Centre, University of Sheffield, Sheffield, UK.
⁸ 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 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology/Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Barcelona, Spain.
¹⁰ Department of Biomedicine, University of Basel, Basel, Switzerland.
¹¹ Department of Biochemistry and Molecular Biology, University of British Columbia and British Columbia Cancer Research Centre, Vancouver, BC, Canada.
¹² Departments of Cell and Tissue Biology, and Anatomy, University of California at San Francisco, San Francisco, CA, USA.
¹³ Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹⁴ 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 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 Centre for Cancer Biology, An alliance of SA Pathology and University of South Australia, Adelaide, SA, Australia.
¹⁷ Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸ School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁹ 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 Department of Cancer Biology, Metastasis Research Center, MD Anderson Cancer Center, Houston, TX, USA.
²¹ Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
²² Centre for Cancer Biology, an Alliance of SA Pathology and the University of South Australia, Adelaide, SA, Australia.
²³ Department of Physics, Northeastern University, Boston, MA, USA.
²⁴ Department of Anatomic Pathology, The Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁵ Department of Medicine (Oncology) and Department of Cell Biology and Physiology, ICCE Institute, Washington University, St. Louis, MO, USA.
²⁶ Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁷ Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁸ Department of Cell and Developmental Biology, University College London, London, UK.
²⁹ Department of Biology, Duke University, Durham, NC, USA.
³⁰ 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 Instituto de Neurociencias (CSIC-UMH) Avda Ramon y Cajal s/n, Sant Joan d´Alacant, Spain.
³³ Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France.
³⁴ Institut Curie, PSL Research University, Paris, France.
³⁵ INSERM UMR 1186, Integrative Tumor Immunology and Genetic Oncology, Gustave Roussy, University Paris-Saclay, Villejuif, France.
³⁶ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³⁷ Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
³⁸ RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
³⁹ 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 School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolloongabba, QLD, Australia.
⁴² Whitehead Institute for Biomedical Research, Department of Biology, MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴³ 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 Department of Computational and Systems Biology and UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
⁴⁵ Department of Molecular and Cellular Biochemistry and UK Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA.
⁴⁶ International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. [email protected].

PMID: 32300252
PMCID: PMC7250738
DOI: 10.1038/s41580-020-0237-9

Erratum in

Author Correction: Guidelines and definitions for research on epithelial-mesenchymal transition.
Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Casanova J, Christofori G, Dedhar S, Derynck R, Ford HL, Fuxe J, García de Herreros A, Goodall GJ, Hadjantonakis AK, Huang RYJ, Kalcheim C, Kalluri R, Kang Y, Khew-Goodall Y, Levine H, Liu J, Longmore GD, Mani SA, Massagué J, Mayor R, McClay D, Mostov KE, Newgreen DF, Nieto MA, Puisieux A, Runyan R, Savagner P, Stanger B, Stemmler MP, Takahashi Y, Takeichi M, Theveneau E, Thiery JP, Thompson EW, Weinberg RA, Williams ED, Xing J, Zhou BP, Sheng G; EMT International Association (TEMTIA). Yang J, et al. Nat Rev Mol Cell Biol. 2021 Dec;22(12):834. doi: 10.1038/s41580-021-00428-9. Nat Rev Mol Cell Biol. 2021. PMID: 34654908 Free PMC article. No abstract available.

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. EMT diversity represented by an epithelial–mesenchymal plasticity model.**
Various cellular features associated with an epithelial or a mesenchymal cell state are found in a range of combinations and to different degrees in cells in different developmental contexts. Epithelial cells are connected with each other via a variety of epithelial cell junctions, including adherens junctions, desmosomes, gap junctions and tight junctions. Adherens junctions are connected to cortical actin bundles, while desmosomes are linked with cytokeratin intermediate filaments. Tight junctions are localized at the apical-lateral contact points in order to help maintain epithelial polarity. Apical–basal polarity guides proper organization of the tight junctions, adherens junctions and desmosomes in epithelial cells. Polarity complexes, including the Par, Crumbs and Scribble complexes, define the apical versus basolateral domains of an epithelial cell. Epithelial cells are attached to the underlying basement membrane via hemidesmosomes, which contain integrin to allow binding to the basement membrane and are also linked to cytokeratins inside the cell. By contrast, mesenchymal cells do not contain functional epithelial junctions and present a back–front polarity in their actin stress fibres. Mesenchymal cells contain vimentin-based intermediate filaments and utilize integrin-containing focal adhesions to attach to the extracellular matrix. The accumulated loss or gain of epithelial/mesenchymal (E/M) characteristics pushes a cell towards various intermediate states (bottom left and right) in a fluid and reversible manner, between a complete epithelial (middle left) and a complete mesenchymal (middle right) state. EMT, epithelial–mesenchymal transition.

**Fig. 2. Growth of the primary literature in EMT.**
The first experimental analysis of epithelial–mesenchymal transition (EMT) in development was published in 1979. The relationship of EMT to growth factors was found in 1989. Transcriptional regulation of EMT was identified in 1994. Subsequent growth of such research was stimulated by linkage of EMT to metastasis, organ fibrosis and stem cells. Growth in the field has been logarithmic since the first TEMTIA meeting in 2003. The graph indicates primary papers published each year, identified by a search of the Web of Science database. The total numbers of publications in 2018 and 2019 exceeded 5,000 and 5,700 articles, respectively. EMT-TF, EMT-associated transcription factors.

See this image and copyright information in PMC

References

1. Hay, E. D. in Epithelial–Mesenchymal Interactions: 18th Hahnemann Symposium (eds R. Fleischmajer & Billingham, R. E.) 31–35 (Williams and Wilkins, 1968).
1. Hay ED. An overview of epithelio–mesenchymal transformation. Acta Anat. 1995;154:8–20. doi: 10.1159/000147748. - DOI - PubMed
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Guidelines and definitions for research on epithelial-mesenchymal transition

Affiliations

Guidelines and definitions for research on epithelial-mesenchymal transition

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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