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Androgen Receptor Signaling Interactions Control Epithelial–Mesenchymal Transition (EMT) in Prostate Cancer Progression

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Androgen-Responsive Genes in Prostate Cancer

Abstract

The role of the androgen receptor (AR) signaling axis in the progression of prostate cancer is a cornerstone to our understanding of the molecular mechanisms behind this important disease. Understanding the innate signaling axis of the AR and the aberrations of this axis in progression of prostate cancer has facilitated the development of emerging therapeutic interventions. Furthermore, the crosstalk of AR with other critical signaling pathways may explain the advancement of prostate cancer to metastatic castration-resistant prostate cancer (CRPC). Of particular interest to such crosstalk are the pathways associated with epithelial to mesenchymal transition (EMT). The reactivation of EMT is a hallmark of metastatic cancer spread, and recent evidence suggests the involvement of AR in the signaling pathways regulating EMT. Cadherin switching, EMT inducing transcription factors, Wnt, TGF-β, and Notch signaling can all be modulated by crosstalk with the AR. Overexpression and localization of the AR to the nucleus has been associated with reactivation of the androgenic signaling axis and progression to metastatic CRPC in patients. In this chapter we consider the current understanding of the functional exchanges between the androgen signaling championed by AR activity and key growth factor signaling pathways that impact EMT towards prostate cancer progression to metastatic CRPC and we discuss the clinical relevance of these insights in the effective targeting of advanced disease.

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Abbreviations

CRPC:

Castration-resistant prostate cancer

ADT:

Androgen deprivation therapy

EMT:

Epithelial–mesenchymal transition

TGF-β:

Transforming growth factor-β

DHT:

Dihydrotestosterone

ARE:

Androgen-responsive elements

PSA:

Prostate-specific antigen

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Acknowledgments

Support: NIH/NIDDK R01 Grant 00491815; James F. Hardymon Research Endowment

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Authors and Affiliations

  1. Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA

    Sarah K. Martin, Michael V. Fiandalo & Natasha Kyprianou

  2. Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA

    Natasha Kyprianou

  3. Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA

    Natasha Kyprianou

  4. University of Kentucky Medical Center, Combs Res. Bldg., Room 306, Lexington, KY, 40536, USA

    Natasha Kyprianou

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    Zhou Wang

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Martin, S.K., Fiandalo, M.V., Kyprianou, N. (2013). Androgen Receptor Signaling Interactions Control Epithelial–Mesenchymal Transition (EMT) in Prostate Cancer Progression. In: Wang, Z. (eds) Androgen-Responsive Genes in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6182-1_15

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