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Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/β-catenin signaling

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Abstract

Background

Recent evidence suggests that the peptidyl-prolyl isomerase Pin1 is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of Pin1 and its function in prostate cancer (PCa) tumor progression.

Methods

Immunohistochemical and quantitative RT-PCR analyses were performed to detect the expression of Pin1 in 86 PCa tissue samples. The functional role of Pin1 was evaluated by small interfering RNA-mediated depletion in PCa cells followed by analyses of cell proliferation and migration. Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D1 was also evaluated.

Results

Our results showed that the high expression of Pin1 staining was 66 of 86 (76.74 %) PCa samples, and in 25 of 86 (29.07 %) BPH tissues, the difference was statistically significant (P < 0.001). Pin1 was significantly elevated in all PCa cell lines when compared to the normal RWPE-1 cells. We observed that proliferation and migration of LNCaP cells were inhibited by Pin1 knockdown. The levels of β-catenin and cyclin D1 in clinical PCa specimens were positively associated with Pin1 expression.

Conclusions

Our results suggest that Pin1 plays an important role in tumorigenesis of PCa, suggesting that targeting Pin1 pathway could represent a potential modality for treating PCa.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  PubMed  Google Scholar 

  2. Zhang L, Yang BX, Zhang HT, Wang JG, Wang HL. Zhao Xj. Prostate cancer: an emerging threat to the health of aging men in Asia. Asian J Androl. 2011;13:574–8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sommariva S, Tarricone R, Lazzeri M, Ricciardi W, Montorsi F. Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2014;. doi:10.1016/j.eururo.2014.11.038.

    PubMed  Google Scholar 

  4. Nakamura K, Greenwood A, Binder L, Bigio EH, Denial S, Nicholson L, et al. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer’s disease. Cell. 2012;149(1):232–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tun-Kyi A, Finn G, Greenwood A, Nowak M, Lee TH, Asara JM, et al. Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nat Immunol. 2011;12(8):733–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Winkler KE, Swenson KI, Kornbluth S, Means AR. Requirement of the prolyl isomerase Pin1 for the replication checkpoint. Science (Wash. DC). 2000;287:1644–7.

    Article  CAS  Google Scholar 

  7. Ayala G, Wang D, Wulf G, Frolov A, Li R, Sowadski J, et al. The prolyl isomerase Pin1 is a novel prognostic marker in human prostate cancer. Cancer Res. 2003;63:6244–51.

    CAS  PubMed  Google Scholar 

  8. Lee TH, Chen CH, Suizu F, Huang P, Schiene-Fischer C, Daum S, et al. Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol Cell. 2011;42(2):147–59.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP, Wang DG. Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol. 2004;164(5):1727–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014;65(1):124–37.

    Article  PubMed  Google Scholar 

  11. Saad F, Pantel K. The current role of circulating tumor cells in the diagnosis and management of bone metastases in advanced prostate cancer. Future Oncol. 2012;8(3):321–31.

    Article  CAS  PubMed  Google Scholar 

  12. Lu KP, Hanes SD, Hunter T. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature. 1996;380:544–7.

    Article  CAS  PubMed  Google Scholar 

  13. Takahashi K, Akiyama H, Shimazaki K, Uchida C, Akiyama-Okunuki H, Tomita M, et al. Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1. Oncogene. 2007;26(26):3835–45.

    Article  CAS  PubMed  Google Scholar 

  14. Liou YC, Zhou XZ, Lu KP. Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins. Trends Biochem Sci. 2011;36:501–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fukuchi M, Fukai Y, Kimura H, Sohda M, Miyazaki T, Nakajima M, et al. Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclin D1 expression. Int J Oncol. 2006;29:329–34.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Affiliated Hospital of Weifang Medical University, No. 2428 Yuhe Road, Kuiwei District, Weifang, Shandong, China

    Z. Zhu, H. Zhang, F. Lang, G. Liu, D. Gao, B. Li & Y. Liu

Authors
  1. Z. Zhu
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  2. H. Zhang
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  3. F. Lang
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  4. G. Liu
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  5. D. Gao
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  6. B. Li
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  7. Y. Liu
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Corresponding author

Correspondence to G. Liu.

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Conflict of interest

The authors have no conflict of interest to declare.

Ethical approval

All specimens were collected in accordance with informed consents of patients, and all procedures complied with the protocol approved by the Ethical Committee of Affiliated Hospital of Weifang Medical University.

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Zhu, Z., Zhang, H., Lang, F. et al. Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/β-catenin signaling. Clin Transl Oncol 18, 792–797 (2016). https://doi.org/10.1007/s12094-015-1431-7

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  • DOI: https://doi.org/10.1007/s12094-015-1431-7

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