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Article

Skp2 is associated with paclitaxel resistance in prostate cancer cells

  • Authors:
    • Yeguo Yang
    • Yi Lu
    • Lihui Wang
    • Atsushi Mizokami
    • Evan T. Keller
    • Jian Zhang
    • Jiejun Fu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi 530021, P.R. China, Department of Urology, Kanazawa University, Kanazawa 920-8641, Japan, Department of Urology and Pathology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA
  • Pages: 559-566
    |
    Published online on: May 13, 2016
       https://doi.org/10.3892/or.2016.4809
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Abstract

Prostate cancer is the most commonly diagnosed tumor in men in the United States. Patients with hormone-refractory prostate cancer are often treated with paclitaxel, but most of them eventually develop drug resistance. S-phase kinase associated protein 2 (Skp2) is a component of the SCF (Skp1-Cullin1-F-box) type of E3 ubiquitin ligase complexes. In the present study, we investigated the role of Skp2 in paclitaxel-resistant DU145-TxR or PC-3-TxR cells by Skp2 silencing or using Skp2 inhibitors. We first confirmed that Skp2 expression is up­regulated in DU145-TxR or PC-3-TxR cells compared with their parental cells DU145 or PC-3, respectively. Knockdown of Skp2 or Skp2 inhibitor treatment in DU145-TxR or PC-3-TxR cells restored paclitaxel sensitivity. E-cadherin was decreased while Vimentin was increased in PC-3-TxR or DU145-TxR cells. In addition, p27 expression was inversely correlated with Skp2 expression in DU145-TxR or PC-3-TxR cells. Moreover, p27 was found to increase in both Skp2 silencing PC-3-TxR and DU145-TxR cells. These results suggest that Skp2 is associated with prostate cancer cell resistance to paclitaxel. Skp2 may be a potential therapeutic target for drug-resistant prostate cancer.
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View References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Pernicová Z, Slabáková E, Kharaishvili G, Bouchal J, Král M, Kunická Z, Machala M, Kozubík A and Souček K: Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Neoplasia. 13:526–536. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Takeda M, Mizokami A, Mamiya K, Li YQ, Zhang J, Keller ET and Namiki M: The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines. Prostate. 67:955–967. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Fujita Y, Kojima K, Ohhashi R, Hamada N, Nozawa Y, Kitamoto A, Sato A, Kondo S, Kojima T, Deguchi T, et al: MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression. J Biol Chem. 285:19076–19084. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW and Kaelin WG Jr: Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature. 428:194–198. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Wang Z, Gao D, Fukushima H, Inuzuka H, Liu P, Wan L, Sarkar FH and Wei W: Skp2: A novel potential therapeutic target for prostate cancer. Biochim Biophys Acta. 1825:11–17. 2012.

7 

Drobnjak M, Melamed J, Taneja S, Melzer K, Wieczorek R, Levinson B, Zeleniuch-Jacquotte A, Polsky D, Ferrara J, Perez-Soler R, et al: Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. Clin Cancer Res. 9:2613–2619. 2003.PubMed/NCBI

8 

Shim EH, Johnson L, Noh HL, Kim YJ, Sun H, Zeiss C and Zhang H: Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate. Cancer Res. 63:1583–1588. 2003.PubMed/NCBI

9 

Lin HK, Chen Z, Wang G, Nardella C, Lee SW, Chan CH, Yang WL, Wang J, Egia A, Nakayama KI, et al: Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature. 464:374–379. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Yang Q, Huang J, Wu Q, Cai Y, Zhu L, Lu X, Chen S, Chen C and Wang Z: Acquisition of epithelial-mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells. Br J Cancer. 110:1958–1967. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Davidovich S, Ben-Izhak O, Shapira M, Futerman B and Hershko DD: Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer. Breast Cancer Res. 10:R632008. View Article : Google Scholar : PubMed/NCBI

12 

Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng Z, Huang HY, Tsai KK, Flores LG, Shao Y, et al: The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell. 149:1098–1111. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Li Y, Mizokami A, Izumi K, Narimoto K, Shima T, Zhang J, Dai J, Keller ET and Namiki M: CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer. Prostate. 70:48–60. 2010. View Article : Google Scholar

14 

Statkiewicz M, Maryan N, Lipiec A, Grecka E, Grygorowicz MA, Omiotek M, Gorska A, Mikula M and Malecki M: The role of the SHH gene in prostate cancer cell resistance to paclitaxel. Prostate. 74:1142–1152. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Singh S, Chitkara D, Mehrazin R, Behrman SW, Wake RW and Mahato RI: Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway. PLoS One. 7:e400212012. View Article : Google Scholar : PubMed/NCBI

16 

Li D, Zhao LN, Zheng XL, Lin P, Lin F, Li Y, Zou HF, Cui RJ, Chen H and Yu XG: Sox2 is involved in paclitaxel resistance of the prostate cancer cell line PC-3 via the PI3K/Akt pathway. Mol Med Rep. 10:3169–3176. 2014.PubMed/NCBI

17 

Kojima K, Fujita Y, Nozawa Y, Deguchi T and Ito M: MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate. 70:1501–1512. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Kim JJ, Yin B, Christudass CS, Terada N, Rajagopalan K, Fabry B, Lee DY, Shiraishi T, Getzenberg RH, Veltri RW, et al: Acquisition of paclitaxel resistance is associated with a more aggressive and invasive phenotype in prostate cancer. J Cell Biochem. 114:1286–1293. 2013. View Article : Google Scholar

19 

Sarikas A, Hartmann T and Pan ZQ: The cullin protein family. Genome Biol. 12:220–232. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Wang X, Li L, Liang Y, Li C, Zhao H, Ye D, Sun M, Jeong LS, Feng Y, Fu S, et al: Targeting the neddylation pathway to suppress the growth of prostate cancer cells: Therapeutic implication for the men's cancer. Biomed Res Int. 2014:9743092014.PubMed/NCBI

21 

Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, et al: Acetylation-dependent regulation of Skp2 function. Cell. 150:179–193. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Li P, Yang R and Gao WQ: Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer. Mol Cancer. 13:552014. View Article : Google Scholar : PubMed/NCBI

23 

Sun Y, Wang BE, Leong KG, Yue P, Li L, Jhunjhunwala S, Chen D, Seo K, Modrusan Z, Gao WQ, et al: Androgen deprivation causes epithelial-mesenchymal transition in the prostate: Implications for androgen-deprivation therapy. Cancer Res. 72:527–536. 2012. View Article : Google Scholar

24 

Kajiyama H, Shibata K, Terauchi M, Yamashita M, Ino K, Nawa A and Kikkawa F: Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol. 31:277–283. 2007.PubMed/NCBI

25 

Zhao H, Bauzon F, Fu H, Lu Z, Cui J, Nakayama K, Nakayama KI, Locker J and Zhu L: Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell. 24:645–659. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Zheng XY, Ding W, Xie LP and Chen ZD: Correlation of Skp2 and P27kip1 protein expression and clinicopathological features of prostate cancer. Ai Zheng. 23:215–218. 2004.In Chinese. PubMed/NCBI

27 

Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N, et al: Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 19:2069–2081. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Zhu L: Skp2 knockout reduces cell proliferation and mouse body size: And prevents cancer? Cell Res. 20:605–607. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Ben-Izhak O, Lahav-Baratz S, Meretyk S, Ben-Eliezer S, Sabo E, Dirnfeld M, Cohen S and Ciechanover A: Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer. J Urol. 170:241–245. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Le TV, Seo Y, Ryu CJ, Lee HR and Park HJ: Increased expression of p27 is associated with the cisplatin resistance in gastric cancer cell line YCC-3. Arch Pharm Res. 33:1127–1132. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Zhao YF, Zhao JY, Yue H, Hu KS, Shen H, Guo ZG and Su XJ: FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27. Biochem Biophys Res Commun. 456:232–237. 2015. View Article : Google Scholar

32 

Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D, et al: Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell. 154:556–568. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Chan CH, Morrow JK, Zhang S and Lin HK: Skp2: A dream target in the coming age of cancer therapy. Cell Cycle. 13:679–680. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Lu Y, Wang L, Mizokami A, Keller ET, Zhang J and Fu J: Skp2 is associated with paclitaxel resistance in prostate cancer cells. Oncol Rep 36: 559-566, 2016.
APA
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E.T., Zhang, J., & Fu, J. (2016). Skp2 is associated with paclitaxel resistance in prostate cancer cells. Oncology Reports, 36, 559-566. https://doi.org/10.3892/or.2016.4809
MLA
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E. T., Zhang, J., Fu, J."Skp2 is associated with paclitaxel resistance in prostate cancer cells". Oncology Reports 36.1 (2016): 559-566.
Chicago
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E. T., Zhang, J., Fu, J."Skp2 is associated with paclitaxel resistance in prostate cancer cells". Oncology Reports 36, no. 1 (2016): 559-566. https://doi.org/10.3892/or.2016.4809
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Lu Y, Wang L, Mizokami A, Keller ET, Zhang J and Fu J: Skp2 is associated with paclitaxel resistance in prostate cancer cells. Oncol Rep 36: 559-566, 2016.
APA
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E.T., Zhang, J., & Fu, J. (2016). Skp2 is associated with paclitaxel resistance in prostate cancer cells. Oncology Reports, 36, 559-566. https://doi.org/10.3892/or.2016.4809
MLA
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E. T., Zhang, J., Fu, J."Skp2 is associated with paclitaxel resistance in prostate cancer cells". Oncology Reports 36.1 (2016): 559-566.
Chicago
Yang, Y., Lu, Y., Wang, L., Mizokami, A., Keller, E. T., Zhang, J., Fu, J."Skp2 is associated with paclitaxel resistance in prostate cancer cells". Oncology Reports 36, no. 1 (2016): 559-566. https://doi.org/10.3892/or.2016.4809
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