A critical role for choline kinase-α in the aggressiveness of bladder carcinomas

Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoK alpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoK alpha show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoK alpha plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoK alpha is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models, including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoK alpha potentiate both tumor formation (P <= 0.0001) and aggressiveness of the disease on different end points (P = 0.011). Accordingly, increased levels of ChoK alpha significantly reduce survival of mice with bladder cancer (P = 0.05). Finally, treatment with a ChoK alpha-specific inhibitor resulted in a significant inhibition of tumor growth (P = 0.02) and in a relevant increase in survival (P = 0.03). Oncogene (2009) 28, 2425-2435; doi:10.1038/onc.2009.91; published online 18 May 2009