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SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival

Oncogene volume 37, pages 3937–3952 (2018)Cite this article

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Abstract

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (Grant nos. 81301688, 81572965, and 81572689), the Innovation-Driven Project of Central South University (Grant no. 2017CX012), the “125 Talent Project” and “New Xiangya Talent Project” of the Third Xiangya Hospital of Central South University, the New Xiangya Talent Projects of the Third Xiangya Hospital of Central South University (Grant no. JY201615), and the Scientific Projects of Health and Family Planning Commision of Hunan Province (Grant no. B2017034).

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Authors and Affiliations

  1. Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    J. Y. Liu, L. Y. He & Y. B. Dai

  2. Institute of Prostate Disease of Central South University, Changsha, Hunan, China

    J. Y. Liu, L. Y. He & Y. B. Dai

  3. Department of Dermatology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    Q. H. Zeng

  4. Department of Onology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    P. G. Cao, Y. X. Zhu, L. Gong & K. Cao

  5. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

    D. Xie

  6. State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China

    D. Xie

  7. School of Public Health, Central South University, Changsha, Hunan, China

    F. Yang

  8. Department of Plastic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    J. J. Li & J. D. Zhou

  9. Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    X. M. Liu

  10. Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha, Hunan, China

    H. L. Zeng

  11. Research Service Office, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    X. J. Fan

  12. Outpatient Service Office, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

    L. Liu

  13. Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China

    Y. Cheng

  14. Department of Tissue-Bank, Hunan Cancer Hospital, Changsha, Hunan, China

    J. Hu

  15. Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, Hunan, China

    H. Bo

  16. Department of Urology, Hunan Cancer Hospital, Changsha, Hunan, China

    Z. Z. Xu

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Correspondence to K. Cao.

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Liu, J.Y., Zeng, Q.H., Cao, P.G. et al. SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival. Oncogene 37, 3937–3952 (2018). https://doi.org/10.1038/s41388-018-0223-2

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