Mechanisms navigating the TGF-β pathway in prostate cancer

Asian Journal of Urology, 2015, 2 (1): 11-18 doi:

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Mechanisms navigating the TGF-β pathway in prostate cancer

Zheng Cao^1,2,3,4, Natasha Kyprianou^1,2,3,4

1. Department of Toxicology, University of Kentucky College of Medicine, Lexington, KY, USA;
2. Department of Urology, University of Kentucky College of Medicine, Lexington, KY, USA;
3. Department of Pathology, University of Kentucky College of Medicine, Lexington, KY, USA;
4. Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA

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Abstract Few pharmacotherapies are currently available to treat castration resistant prostate cancer (CRPC), with low impact on patient survival. Transforming growth factor-β (TGF-b) is a multi-functional peptide with opposite roles in prostate tumorigenesis as an inhibitor in normal growth and early stage disease and a promoter in advanced prostate cancer. Dysregulated TGF-β signaling leads to a cascade of events contributing to oncogenesis, including upregulated proliferation, decreased apoptosis, epithelial-to-mesenchymal transition (EMT) and evasion of immune surveillance. TGF-β signaling pathway presents an appropriate venue for establishing a therapeutic targeting platform in CRPC. Exploitation of TGF-β effectors and their cross talk with the androgen axis pathway will provide new insights into mechanisms of resistance of the current antiandrogen therapeutic strategies and lead to generation of new effective treatment modalities for CRPC. Points of functional convergence of TGF-β with key oncogenic pathways, including mitogen-activated protein kinase (MAPK) and androgen receptor (AR), are discussed as navigated within the EMT landscape in the tumor microenvironment. In this context the emerging anti-TGF-β pharmacotherapies for prostate cancer treatment are considered. Targeting the functional cross-talk between the TGF-β signaling effectors with the androgen axis supports the development of novel therapeutic strategies for treating CRPC with high specificity and efficacy in a personalized-medicine approach.

Key words： Transforming growth factor-b Prostate tumors Androgen receptor Epithelialmesenchymal transition Therapeutic value

Received: 15 July 2014 Published: 06 February 2015

Fund:This work was supported by an NIH grant (RO1 DK 083761).

Corresponding Authors: Natasha Kyprianou E-mail: nkypr2@uky.edu

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Zheng Cao,Natasha Kyprianou. Mechanisms navigating the TGF-β pathway in prostate cancer[J]. Asian Journal of Urology, 2015, 2(1): 11-18.

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http://www.ajurology.com/EN/ OR http://www.ajurology.com/EN/Y2015/V2/I1/11

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