Signaling mechanisms of the epithelial-mesenchymal transition
By David M. Gonzalez, D. Medici. Science Signaling, 2014
1,547 citations recorded by the source corpus.
Signals from the microenvironment trigger epithelial-mesenchymal transition in development and disease through multiple, crosstalking pathways. The epithelial-mesenchymal transition (EMT) is a process of cellular plasticity that critically mediates embryonic development and tissue repair, as well as the progression of diseases like organ fibrosis and cancer metastasis. In this review, which contains 7 figures and 261 references, Gonzalez and Medici describe the intracellular pathways and extracellular signals that regulate gene expression to induce EMT in development, physiology, and disease. 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.
Subfields: Genetics, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/7e0a7582a8b1f5d387457fde8f75a9d079e2c985
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In Molecular Biology
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In Oncology
Citations in the corpus
- Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer (2016, background): “Several key signaling pathways, including transforming growth factor beta (TGFβ), Wnt, Notch and Hedgehog, are known to be involved in EMT [8].”
- The basics of epithelial–mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective (2019, background): “…Frizzled receptors, it enhances Dvl‐dependent an inhibition of GSK‐3β, a kinase that helps in a reduction of cytoplasmic β‐catenin (Bryan et al., 2009; Gonzalez & Medici, 2015; Sastre-Perona & Santisteban, 2012) [Color figure can be viewed at wileyonlinelibrary.com] localization of β‐catenin to…”
- Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation (2018, result): “This is again consistent with other GSEA results, as both signaling pathways are known mediators of the EMT mechanism (Gonzalez and Medici, 2014).”
- TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis (2019, background): “) by several complexes, such as ZEB1/2, the SNAIL1-SMAD3/4 complex, the β-catenin-SMAD2 complex, the LEF1-SMAD3/4 complex and the SMAD3-AP1-1 complex [85].”