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Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle?

Nature Reviews Urology volume 8, pages 428–439 (2011)Cite this article

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Abstract

The lethal consequences of prostate cancer are related to its metastasis to other organ sites. Epithelial-to-mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm to explain invasive and metastatic behavior during cancer progression. EMT is a normal physiologic process by which cells of epithelial origin convert into cells bearing mesenchymal characteristics. It has been proposed that EMT is co-opted by cancer cells during their metastatic dissemination from a primary organ to secondary sites, but the extent to which this recapitulates physiologic EMT remains uncertain. However, there is ample evidence that EMT-like states occur in, and may contribute to, prostate cancer progression and metastasis, and so has become a very active area of research. Here we review this evidence and explore recent studies that have aimed to better define the role and mechanisms of EMT in prostate cancer. While definitive evidence of something akin to physiologic EMT is still lacking in human prostate cancer, this area of research has nonetheless provided new avenues of investigation into the longstanding puzzles of metastasis, therapeutic resistance, and prognostic biomarkers.

Key Points

  • Epithelial-to-mesenchymal transition (EMT) is a normal physiologic process that involves lineage-specific, reversible transdifferentiation of epithelial cells in response to local inductive stimuli

  • Prostate cancers exhibit EMT-like states, characterized by changes in the expression of various markers, such as E-cadherin and vimentin, which are associated with invasive behavior

  • Many mechanisms have been reported to produce EMT-like states in prostate cancer

  • The degree to which EMT-like states in prostate cancer result from processes similar to those that produce physiologic EMT is unclear

  • EMT-like states are associated with metastatic behavior and therapeutic resistance, so are potential targets for biomarker development or novel therapeutics

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Figure 1: True and apparent EMT might both contribute to metastasis, yet be difficult to distinguish.
Figure 2: Many roads lead to EMT: the molecular basis for the mechanisms of EMT and EMT-like states.
Figure 3: The possible roles of EMT-like states in the metastatic cascade.

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Acknowledgements

We would like to thank members of the Henry laboratory and Dr. Christopher Stipp for critical reading of the manuscript, and Dr. Beatrice Knudsen for sharing unpublished results. Work related to this topic in the Henry laboratory has been supported by NIH grant RO1 CA130916 and DOD grant W81XWH-10-1-0313. We apologize to colleagues whose work we were unable to cite due to space constraints.

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  1. Department of Molecular Physiology and Biophysics and Pathology, Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine and Holden Comprehensive Cancer Center, The University of Iowa, Bowen Science Building, 51 Newton Road, Iowa City, 52242, IA, USA

    Jones T. Nauseef & Michael D. Henry

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  1. Jones T. Nauseef
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  2. Michael D. Henry
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Both authors contributed equally to researching data, discussing the content, writing the article and performing review/editing of the manuscript before submission.

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Correspondence to Michael D. Henry.

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Nauseef, J., Henry, M. Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle?. Nat Rev Urol 8, 428–439 (2011). https://doi.org/10.1038/nrurol.2011.85

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