Abstract
Epithelial–mesenchymal transition (EMT) is a phenotypic conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes, such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, and is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bidirectional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of RAS-controlled signaling mediators, ERK1, ERK2 and phosphatidylinositol 3-kinase, as microenvironmental responsive regulators of EMT.
Key Points
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Fibroblast activity (e.g. desmoplasia and stromal transcriptomes) are associated with poor outcome in cancers
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Epithelial–mesenchymal transition (EMT) of epithelial cancer cells contributes to this activity in the peritumor stroma, and EMT is a subset of the more generalized cell phenotype plasticity exhibited by aggressive tumor cells
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Clear evidence for EMT of tumor cells in human tumors is rare, and this might be owing to its transient and dynamic nature
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The clinical significance of EMT is still under study but has been associated with the metastatic/invasive phenotype and specific breast carcinoma subtypes
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Study of EMT has focused on its role in active dissemination of tumor cells (e.g. migration and invasion), but emerging evidence suggests a broader functional role in tumor progression, including drug resistance and immune modulation
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RAS-regulated pathways connect regulation of EMT to the tumor microenvironment
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Turley, E., Veiseh, M., Radisky, D. et al. Mechanisms of Disease: epithelial–mesenchymal transition—does cellular plasticity fuel neoplastic progression?. Nat Rev Clin Oncol 5, 280–290 (2008). https://doi.org/10.1038/ncponc1089
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DOI: https://doi.org/10.1038/ncponc1089
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