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Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance

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Prostate Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1210))

Abstract

Metastatic or locally advanced prostate cancer (PCa) is typically treated with androgen deprivation therapy (ADT). Initially, PCa responds to the treatment and regresses. However, PCa almost always develops resistance to androgen deprivation and progresses to castrate-resistant prostate cancer (CRPCa), a currently incurable form of PCa. Wnt/β-Catenin signaling is frequently activated in late stage PCa and contributes to the development of therapy resistance. Although activating mutations in the Wnt/β-Catenin pathway are not common in primary PCa, this signaling cascade can be activated through other mechanisms in late stage PCa, including cross talk with other signaling pathways, growth factors and cytokines produced by the damaged tumor microenvironment, release of the co-activator β-Catenin from sequestration after inhibition of androgen receptor (AR) signaling, altered expression of Wnt ligands and factors that modulate the Wnt signaling, and therapy-induced cellular senescence. Research from genetically engineered mouse models indicates that activation of Wnt/β-Catenin signaling in the prostate is oncogenic, enables castrate-resistant PCa growth, induces an epithelial-to-mesenchymal transition (EMT), promotes neuroendocrine (NE) differentiation, and confers stem cell-like features to PCa cells. These important roles of Wnt/β-Catenin signaling in PCa progression underscore the need for the development of drugs targeting this pathway to treat therapy-resistant PCa.

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Author information

Authors and Affiliations

  1. Department of Pathology, Overton Brooks Medical Center, Shreveport, LA, USA

    Yunshin Yeh

  2. Merton College, University of Oxford, Oxford, UK

    Qiaozhi Guo

  3. Department of Biochemistry & Molecular Biology, LSU Health Sciences Center, Shreveport, LA, USA

    Zachary Connelly, Siyuan Cheng, Shu Yang, Nestor Prieto-Dominguez & Xiuping Yu

  4. Department of Urology, LSU Health Sciences Center, Shreveport, LA, USA

    Xiuping Yu

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  1. Yunshin Yeh
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  2. Qiaozhi Guo
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  3. Zachary Connelly
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  4. Siyuan Cheng
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  5. Shu Yang
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  6. Nestor Prieto-Dominguez
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  7. Xiuping Yu
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Correspondence to Xiuping Yu .

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  1. Department of Laboratory Medicine and Pathology, Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott M. Dehm

  2. Departments of Urology, and Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Donald J. Tindall

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Yeh, Y. et al. (2019). Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance. In: Dehm, S., Tindall, D. (eds) Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1210. Springer, Cham. https://doi.org/10.1007/978-3-030-32656-2_16

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