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Mechanisms of Disease: epithelial–mesenchymal transition—does cellular plasticity fuel neoplastic progression?

Nature Clinical Practice Oncology volume 5, pages 280–290 (2008)Cite this article

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

  • Fibroblast activity (e.g. desmoplasia and stromal transcriptomes) are associated with poor outcome in cancers

  • 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

  • Clear evidence for EMT of tumor cells in human tumors is rare, and this might be owing to its transient and dynamic nature

  • The clinical significance of EMT is still under study but has been associated with the metastatic/invasive phenotype and specific breast carcinoma subtypes

  • 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

  • RAS-regulated pathways connect regulation of EMT to the tumor microenvironment

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Figure 1: Common morphologic characteristics of epithelial and mesenchymal cells.
Figure 2: EMT of mammary epithelial cells.
Figure 3: The dynamic role of EMT in mammary gland neoplastic processes.
Figure 4: Overlap between the EMT gene signature of EpH4 mammary cells and that of the embryonic palate.
Figure 5: Microenvironmental and spatial regulation of signaling pathways controlling EMT.

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Authors and Affiliations

  1. EA Turley is a Distinguished Oncology Scientist and Professor at the London Health Sciences Centre and University of Western Ontario, London, ON, Canada,

    Eva A Turley

  2. DC Radisky is an Assistant Professor at the Mayo Clinic Cancer Center, Jacksonville, FL, USA.,

    Derek C Radisky

  3. M Veiseh is a Postdoctoral Fellow in the Life Sciences Division, at the Lawrence Berkeley National Laboratory, Berkeley, CA, USA.,

    Mandana Veiseh

  4. MJ Bissell is Distinguished Scientist and Director of the Life Sciences Division, at the Lawrence Berkeley National Laboratory, Berkeley, CA, USA.,

    Mina J Bissell

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Correspondence to Mina J Bissell.

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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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