B7-homolog 4 promotes epithelial-mesenchymal transition and invasion of bladder cancer cells via activation of nuclear factor- κB.

This study was conducted to explore the biological role of B7-H4 in the aggressiveness of bladder cancer and 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-κB signaling. Pharmacological inhibition of NF-κB partially prevented B7-H4-mediated bladder cancer cell invasion. Taken together, the B7-H4/NF-κB signaling is involved in the EMT and invasion of bladder cancer cells and represents a new candidate target for the treatment of bladder cancer. PMID: 29391086 [PubMed - as supplied by publisher]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research