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J Cancer 2018; 9(24):4774-4782. doi:10.7150/jca.25811 This issue Cite

Research Paper

Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway

Jin-Bo Chen1*, Meng Zhang2*, Xiao-Long Zhang3, Yu Cui1, Pei-Hua Liu1, Jiao Hu1, Hui-Huang Li1, Hang Jin1, Long-Fei Liu1, Min-Feng Chen1, He-Qun Chen1, Chao-Zhao Liang2✉, Xiong-Bing Zu1✉

1. Department of Urology, Xiangya Hospital, Central South University, NO. 87 Xiangya Road, Changsha, Hunan 410008, P.R. China
2. Department of Urology, the First Affiliated Hospital of Anhui Medical University, NO. 218 Jixi Road, Hefei, Anhui 230022, P.R. China
3. Department of Experimental Research, Sun Yat-Sen University Cancer Center, NO.651 East Dongfeng Road, Guangzhou, Guangdong 510060, P.R. China
*These authors contributed equally to this work.

✉ Corresponding authors: Xiong-Bing Zu, M.D., Ph.D., Department of Urology, Xiangya Hospital, Central South University, NO.87 Xiangya Road, Changsha, Hunan, P.R. China, E-mail: whzuxbcom or Chao-Zhao Liang, M.D., Ph.D., Department of Urology, the More

Citation:
Chen JB, Zhang M, Zhang XL, Cui Y, Liu PH, Hu J, Li HH, Jin H, Liu LF, Chen MF, Chen HQ, Liang CZ, Zu XB. Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway. J Cancer 2018; 9(24):4774-4782. doi:10.7150/jca.25811. https://www.jcancer.org/v09p4774.htm
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Abstract

Background: Bladder cancer is one of the most common malignancies in urologic system. The glucocorticoid-inducible kinase 2 (SGK2) expression and function were largely unknown in cancers. Current study was aimed to investigate the role of SGK2 in bladder cancer and its potential mechanisms.

Methods: SGK2 expression was quantified by western blot (WB) in multiple bladder cancer cell lines (T24, 5637, J82 and UMUC3) compared with normal urothelial cell line (SVHUC). SGK2 knocking down and overexpression model were established by lentivirus transfection. MTT, colony formation, wound healing and transwell assay were used to assess the tumor cell proliferation, migration and invasion abilities, respectively. In addition, molecular function analysis was performed using FunRich software V3. Immunoprecipitation (IP) assay was applied to investigate the interaction between SGK2 and β-catenin at protein level. TCGA database was retrieved to verify the association between these genes and clinical tumor stage as well as prognosis among bladder cancer patients.

Results: SGK2 expression was significantly upregulated in multiple bladder cancer cell lines compared with SVHUC at protein level. Cell proliferation, migration and invasion abilities were significantly decreased after knocking down SGK2 in J82 and UMUC3 cell lines. Inversely, cell aggressive phenotypes were significantly increased after overexpressing SGK2 in T24 cell line. Furthermore, functional analyses of SGK2 based on TCGA database showed that SGK2 related genes were involved in receptor activity, ATP binding, DNA repair protein, trans-membrane receptor activity and lipid binding. In addition, protein interaction analysis identified c-Myc was significantly enriched in SGK2 positively associated genes. The prediction was validated by WB and IP assay that SGK2 could directly bind with β-catenin at protein level to regulate their downstream gene c-Myc expression in bladder cancer to influence tumor progression. And clinical data generated from TCGA database also identified these downstream genes were significantly associated with tumor stage and survival status of bladder cancer patients.

Conclusion: Taken together, our findings suggest SGK2 promotes bladder cancer progression via mediating β-catenin/c-Myc signaling pathway, which may serve as a potential therapeutic target for bladder cancer patients.

Keywords: glucocorticoid-inducible kinase 2, bladder cancer, c-Myc, β-catenin

Citation styles

APA
Chen, J.B., Zhang, M., Zhang, X.L., Cui, Y., Liu, P.H., Hu, J., Li, H.H., Jin, H., Liu, L.F., Chen, M.F., Chen, H.Q., Liang, C.Z., Zu, X.B. (2018). Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway. Journal of Cancer, 9(24), 4774-4782. https://doi.org/10.7150/jca.25811.

ACS
Chen, J.B.; Zhang, M.; Zhang, X.L.; Cui, Y.; Liu, P.H.; Hu, J.; Li, H.H.; Jin, H.; Liu, L.F.; Chen, M.F.; Chen, H.Q.; Liang, C.Z.; Zu, X.B. Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway. J. Cancer 2018, 9 (24), 4774-4782. DOI: 10.7150/jca.25811.

NLM
Chen JB, Zhang M, Zhang XL, Cui Y, Liu PH, Hu J, Li HH, Jin H, Liu LF, Chen MF, Chen HQ, Liang CZ, Zu XB. Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway. J Cancer 2018; 9(24):4774-4782. doi:10.7150/jca.25811. https://www.jcancer.org/v09p4774.htm

CSE
Chen JB, Zhang M, Zhang XL, Cui Y, Liu PH, Hu J, Li HH, Jin H, Liu LF, Chen MF, Chen HQ, Liang CZ, Zu XB. 2018. Glucocorticoid-Inducible Kinase 2 Promotes Bladder Cancer Cell Proliferation, Migration and Invasion by Enhancing β-catenin/c-Myc Signaling Pathway. J Cancer. 9(24):4774-4782.

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