The role of ILK in bladder cancer

Integrin linked kinase (ILK) is an essential transducer of integrin signals, and its protein levels and activity are often elevated in solid tumours. Inhibition of ILK activity blocks cell migration, making it an attractive target for development of anti-cancer therapeutics. Almost nothing is known about the role of ILK in bladder cancer, however, and we sought to determine the role of ILK in critical oncogenic functions of bladder cancer cells.

Western blot analyses showed that ILK was expressed in bladder cancer cell lines. In order to investigate the role of ILK in bladder cancer we employed a siRNA strategy to knock down ILK expression and inhibit its kinase and scaffolding activities. ILK knockdown did not affect cell proliferation or apoptosis. By contrast, ILK knockdown significantly reduced cell migration and integrin dependent actin cytoskeleton reorganization, concomitant with impairment of Rac1 membrane targeting. This suggests an important role for the ILK-binding partner α-parvin in bladder cancer cell migration. Indeed, α-parvin knockdown using RNAi led to a dramatic change in cell shape, and cells were not able to spread on the integrin substrate fibronectin. In addition to Rac-GTP loading via ILK/Parvin/ αPIX complex, ILK also regulates Rac1 membrane translocation which is critical for the initiation of downstream effectors signaling.
Our data reveal a critical role for α-parvin in spreading and migration of bladder cancer cells and suggests ILK is a viable target for therapeutic development in bladder cancer.

No relevant conflicts of interest declared.