Bladder cancer is the seventh most common cancer in the world and is staged via the tumour node metastasis system, which describes the extent of invasion. This classification divides the carcinoma into non-muscle invasive bladder cancer and muscle invasive bladder cancer, which accounts for 30% of cases and has a five year survival rate of less than 50%. Better understanding of the mechanism of bladder cancer tumorigenesis and progression can help to discover novel and effective treatment strategies.
TBK1, a non-canonical member of the IKK kinase family, plays a critical role in innate immunity and inflammation. TBK1 has been found to activate the transcription factor IRF3, leading to the production of type I IFNs and other cytokines of the immediate early host defence response. Mounting evidence implicates TBK1 plays a role in oncogenic signalling and tumorigenesis. Recent studies have found that expression of TBK1 is increased in breast, lung and colon cancers.
A new study led by Dr. Wei Chen at the First Affiliated Hospital of Shenzhen University in China found non-canonical IkB kinase TBK1 is up-regulated in bladder cancer tissue and cell lines. Knockdown of TBK1 markedly inhibits cell proliferation and migration. Furthermore, inhibition of TBK1 kinase activity by BX795 significantly attenuates bladder cancer cell proliferation and migration. Researchers also observed that the over expression of TBK1 promoted the phosphorylation of Akt, whereas knockdown of TBK1 reverses this action.
The data from this study suggests that TBK1 modulates the malignant behaviours of bladder cancer cell via Akt signalling, revealing new insights in discovering new therapy target for bladder cancer.