Activation of nuclear factor κB pathway and downstream targets survivin and livin by SHARPIN contributes to the progression and metastasis of prostate cancer

Authors

  • Yiming Zhang MD,

    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    2. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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    • The first 3 authors contributed equally to this work.

  • Hai Huang MD, PhD,

    Corresponding author
    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    • Corresponding author: Hai Huang, MD, PhD, Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 W. Yanjiang Road, Guangzhou 510120, People's Republic of China; Fax: (011) 86-20-81332336; huanghai257@126.com, and Zhenghui Guo, MD, PhD, Department of Urology, Sun Yat-Sen Memorial Hospital, BoJi-Affiliated Hospital, Sun Yat-Sen University, 107 W. Yanjiang Road, Guangzhou 510120, People's Republic of China; Fax: (011) 86-20-81332336;2352236171@qq.com

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    • The first 3 authors contributed equally to this work.

  • Huimin Zhou MD,

    1. Department of Gastroenterology, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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    • The first 3 authors contributed equally to this work.

  • Tao Du MD,

    1. Prenatal Diagnosis Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Lexiang Zeng MM,

    1. Department of Pediatric Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Yi Cao MM,

    1. Department of Emergency, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Jieqing Chen MM,

    1. Department of Urology, Second People's Hospital of Shenzhen, Shenzhen, China
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  • Yiming Lai MM,

    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Jin Li MM,

    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Ganping Wang MM,

    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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  • Zhenghui Guo MD, PhD

    Corresponding author
    1. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
    • Corresponding author: Hai Huang, MD, PhD, Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 W. Yanjiang Road, Guangzhou 510120, People's Republic of China; Fax: (011) 86-20-81332336; huanghai257@126.com, and Zhenghui Guo, MD, PhD, Department of Urology, Sun Yat-Sen Memorial Hospital, BoJi-Affiliated Hospital, Sun Yat-Sen University, 107 W. Yanjiang Road, Guangzhou 510120, People's Republic of China; Fax: (011) 86-20-81332336;2352236171@qq.com

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Errata

This article is corrected by:

  1. Errata: Erratum: Activation of nuclear factor κB pathway and downstream targets survivin and livin by SHARPIN contributes to the progression and metastasis of prostate cancer Article first published online: 27 December 2016

  • We thank Dr. Wang He and Dr. Pei Wang for reviewing this article.

Abstract

BACKGROUND

Nuclear factor κB (NFκB) signaling is strongly associated with tumor progression, and studies have shown that SHANK-associated RH domain interacting protein (SHARPIN) is crucial for NFκB pathway activation. However, the expression and functions of SHARPIN in prostate cancer (PCa) have not yet been defined.

METHODS

The expression of SHARPIN in PCa cell lines and tissues was evaluated with western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. After SHARPIN was silenced in the PCa cell lines, western blots were used to confirm that SHARPIN physically associated with components of the NFκB pathway and the downstream targets (survivin and livin). The functions of SHARPIN in cell proliferation, migration, and invasion in vitro were measured with 5-(3-carboxymethoxyphenyl)-2-(4,5-dimenthylthiazoly)-3-(4-sulfophenyl)tetrazolium, inner salt (MTS), Transwell, and invasion assays, respectively. Flow cytometry was employed to evaluate cell apoptosis. Furthermore, tumorigenesis in vivo was examined with tumorigenicity assays.

RESULTS

SHARPIN expression was upregulated in PCa cell lines and tissues. The knockdown of SHARPIN or incubation with Bay 11-7082 (an NFκB inhibitor) led to dramatically decreased levels of phosphorylated IκBα and phosphorylated p65 in comparison with the control group. Downregulation of survivin and livin due to SHARPIN inhibition was attributable to transcriptional repression (P < .05). Decreases in cell viability, migration, invasion, and survival with a higher sensitivity to docetaxel in vitro and with repressed tumorigenesis in vivo were observed upon SHARPIN silencing, and this was consistent with the results from inhibition of the NFκB pathway and its downstream targets.

CONCLUSION

The current study demonstrates that overexpression of SHARPIN promotes activation of the NFκB pathway and downstream targets survivin and livin, which potentially contributes to PCa development. Cancer 2014;120:3208–3218. ©2014 American Cancer Society.

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