Signaling mechanisms of the epithelial-mesenchymal transition
TLDR
This review discusses how intracellular pathways and extracellular signals that regulate gene expression to induce EMT crosstalk and respond to signals from the microenvironment to regulate the expression and function of EMT-inducing transcription factors in development, physiology, and disease.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.read more
Citations
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New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer
TL;DR: It is highlighted 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, and its effects on the immunobiology of carcinomas.
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Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
Tathiane M. Malta,Artem Sokolov,Andrew J. Gentles,Tomasz Burzykowski,Laila M. Poisson,John N. Weinstein,Bozena Kaminska,Joerg Huelsken,Larsson Omberg,Olivier Gevaert,Antonio Colaprico,Patrycja Czerwińska,Sylwia Mazurek,Lopa Mishra,Holger Heyn,Alexander Krasnitz,Andrew K. Godwin,Alexander J. Lazar,Joshua M. Stuart,Katherine A Hoadley,Peter W. Laird,Houtan Noushmehr,Maciej Wiznerowicz +22 more
TL;DR: Novel stemness indices for assessing the degree of oncogenic dedifferentiation are provided and it is found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors.
Functional genomics reveals a bmp driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming (oral presentation)
TL;DR: In this article, the authors explored the molecular mechanisms underlying the reprogramming process by exploiting a secondary mouse embryonic fibroblast model that forms iPSCs with high efficiency upon inducible expression of Oct4, Klf4, c-Myc, and Sox2.
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TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis
TL;DR: The role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis is considered and recent insights into the multistep and dynamically controlled process of T GF-β-induced EMT are highlighted.
Journal ArticleDOI
Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer
Bowen Du,Joong Sup Shim +1 more
TL;DR: The mechanism by which EMT contributes to drug resistance in cancer cells is described and new advances in research in EMT-associated drug resistance are summarized.
References
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Raghu Kalluri,Robert A. Weinberg +1 more
TL;DR: Processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias and the identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes.
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Cell signaling by receptor-tyrosine kinases
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.