title: Signaling mechanisms of the epithelial-mesenchymal transition.
abstract: The epithelial-mesenchymal transition (EMT) is an essential mechanism in embryonic development and tissue repair. EMT also contributes to the progression of disease, including organ fibrosis and cancer. EMT, as well as a similar transition occurring in vascular endothelial cells called endothelial-mesenchymal transition (EndMT), results from the induction of transcription factors that alter gene expression to promote loss of cell-cell adhesion, leading to a shift in cytoskeletal dynamics and a change from epithelial morphology and physiology to the mesenchymal phenotype. Transcription program switching in EMT is induced by signaling pathways mediated by transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP), Wnt-β-catenin, Notch, Hedgehog, and receptor tyrosine kinases. These pathways are activated by various dynamic stimuli from the local microenvironment, including growth factors and cytokines, hypoxia, and contact with the surrounding extracellular matrix (ECM). We discuss how these pathways crosstalk and respond to signals from the microenvironment to regulate the expression and function of EMT-inducing transcription factors in development, physiology, and disease. Understanding these mechanisms will enable the therapeutic control of EMT to promote tissue regeneration, treat fibrosis, and prevent cancer metastasis.
authors.affiliation: Departments of Orthopaedics and Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Center for Regenerative Medicine, Rhode Island Hospital, Providence, RI 02903, USA. Cardiovascular Research Center, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gonzalez
authors.affiliation: Departments of Orthopaedics and Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Center for Regenerative Medicine, Rhode Island Hospital, Providence, RI 02903, USA. Cardiovascular Research Center, Rhode Island Hospital, Providence, RI 02903, USA. damian_medici@brown.edu.
authors.forename: Damian
authors.initials: D
authors.lastname: Medici
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics; D060833:Cellular Microenvironment; D003599:Cytoskeleton / Q000648:ultrastructure; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology; D010641:Phenotype; D020239:Receptor Cross-Talk / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases