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B7-Homolog 4 Promotes Epithelial–Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB

Haoran Wu1, Xugang Wang1, Naixin Mo, Liang Zhang, Xiaoliang Yuan, Zhong Lü

Department of Urology, Wujin Hospital, Affiliated to Jiangsu University, Changzhou, P.R. China

Oncology Research 2018, 26(8), 1267-1274. https://doi.org/10.3727/096504018X15172227703244

Abstract

B7-homolog 4 (B7-H4), a member of the B7 family of costimulatory molecules, has been reported to be upregulated in urothelial cell carcinoma. This study was conducted to explore the biological role of B7-H4 in the aggressiveness of bladder cancer and the associated molecular mechanism. We found that the mRNA and protein levels of B7-H4 were significantly greater in bladder cancer cell lines than in SV-HUC-1 (normal human urothelial cells). Overexpression of B7-H4 significantly promoted bladder cancer cell migration and invasion, whereas knockdown of B7-H4 exerted an opposite effect. However, the growth of bladder cancer cells was not altered by B7-H4 overexpression or knockdown. Overexpression of B7-H4 promoted epithelial– mesenchymal transition (EMT), as evidenced by decreased E-cadherin and increased vimentin expression. The EMT inducers Twist1 and Snail were upregulated by B7-H4 overexpression and downregulated by B7-H4 silencing. Mechanistically, overexpression of B7-H4 induced the activation of NF-kB signaling. Pharmacological inhibition of NF-kB partially prevented B7-H4-mediated bladder cancer cell invasion. Taken together, B7-H4/NF-kB signaling is involved in the EMT and invasion of bladder cancer cells and represents a new candidate target for the treatment of bladder cancer.

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APA Style
Wu, H., Wang, X., Mo, N., Zhang, L., Yuan, X. et al. (2018). B7-homolog 4 promotes epithelial–mesenchymal transition and invasion of bladder cancer cells via activation of nuclear factor-κb. Oncology Research, 26(8), 1267-1274. https://doi.org/10.3727/096504018X15172227703244
Vancouver Style
Wu H, Wang X, Mo N, Zhang L, Yuan X, Lü Z. B7-homolog 4 promotes epithelial–mesenchymal transition and invasion of bladder cancer cells via activation of nuclear factor-κb. Oncol Res. 2018;26(8):1267-1274 https://doi.org/10.3727/096504018X15172227703244
IEEE Style
H. Wu, X. Wang, N. Mo, L. Zhang, X. Yuan, and Z. Lü "B7-Homolog 4 Promotes Epithelial–Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB," Oncol. Res., vol. 26, no. 8, pp. 1267-1274. 2018. https://doi.org/10.3727/096504018X15172227703244



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