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RETRACTED ARTICLE: CIP2A mediates prostate cancer progression via the c-Myc signaling pathway

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Tumor Biology

This article was retracted on 20 April 2017

Abstract

Recent evidence suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of CIP2A and its function in our large collection of prostate samples. Between August 2000 and December 2013, 126 patients with histologically confirmed prostate cancer (PCa) and 92 with benign prostate hyperplasia (BPH) were recruited into the study. Quantitative real-time PCR (RT-PCR), Western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in PCa clinical samples and cell lines. The relationships between CIP2A expression and clinicopathological features were analyzed. The functional role of CIP2A in PCa cells was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. High expression of CIP2A staining was 86.51 % (109/126) in 126 cases of PCa and 17.39 % (16/92) in 92 cases of BPH; the difference of CIP2A expression between PCa and BPH was statistically significant. CIP2A was significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells at both the messenger RNA (mRNA) and protein levels. Silencing of CIP2A inhibited the proliferation of DU-145 cells which have a relatively high level of CIP2A in a time- and concentration-dependent manner, and the invasion and migration of DU-145 cells were distinctly suppressed. Furthermore, CIP2A knockdown led to substantial reductions in c-Myc levels in DU-145 cells, but no significant change in phosphorylated Akt expression after CIP2A knockdown in DU-145 cells. Our data suggest that the pathogenesis of human PCa maybe mediated by CIP2A, and CIP2A inhibition treatment may provide a promising strategy for the antitumor therapy of PCa, and thus, CIP2A could represent selective targets for the molecularly targeted treatments of PCa.

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References

  1. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.

    Article  CAS  PubMed  Google Scholar 

  2. Ren SC, Chen R, Sun YH. Prostate cancer research in China. Asian J Androl. 2013;15:350–53.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localized disease. Eur Urol. 2011;59(1):61–71.

    Article  PubMed  Google Scholar 

  4. 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 

  5. Lassi K, Dawson NA. Emerging therapies in castrate-resistant prostate cancer. Curr Opin Oncol. 2009;21:260–5.

    Article  CAS  PubMed  Google Scholar 

  6. Li W, Ge Z, Liu C, Liu Z, Bjorkholm M, Jia J, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14:3722–8.

    Article  CAS  PubMed  Google Scholar 

  7. Junttila MR, Puustinen P, Niemela M, Ahola R, Arnold H, Bottzauw T, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51–62.

    Article  CAS  PubMed  Google Scholar 

  8. Khanna A, Bockelman C, Hemmes A, Junttila MR, Wiksten JP, Lundin M, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101:793–805.

    Article  CAS  PubMed  Google Scholar 

  9. Come C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15:5092–100.

    Article  CAS  PubMed  Google Scholar 

  10. Qu YY, Dai B, Kong YY, Ye DW, Yao XD, et al. Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy. Asian J Androl. 2013;15(1):110–5.

    Article  CAS  PubMed  Google Scholar 

  11. Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20.

    Article  CAS  PubMed  Google Scholar 

  12. Wiegering A, Pfann C, Uthe FW, Otto C, Rycak L, Mäder U, et al. CIP2A influences survival in colon cancer and is critical for maintaining Myc expression. PLoS One. 2013;8(10):e75292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hemmes A, Leminen A, Westermarck J, Haglund C, Butzow R, et al. Prognostic role of CIP2A expression in serous ovarian cancer. Br J Cancer. 2011;105(7):989–95.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ren J, Li W, Yan L, Jiao W, Tian S, et al. Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients survival. Br J Cancer. 2011;105(12):1905–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, et al. A signaling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 2004;6:308–18.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the grants from the Science and Technology Research Projects of Guangzhou (No. 11A72070508).

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Correspondence to Zexuan Su.

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The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

An erratum to this article is available at http://dx.doi.org/10.1007/s13277-017-5487-6.

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Guo, Z., Liu, D. & Su, Z. RETRACTED ARTICLE: CIP2A mediates prostate cancer progression via the c-Myc signaling pathway. Tumor Biol. 36, 4777–4783 (2015). https://doi.org/10.1007/s13277-015-3129-4

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  • DOI: https://doi.org/10.1007/s13277-015-3129-4

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