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

E. Hernando, J. Sarmentero-Estrada, T. Koppie, C. Belda-Iniesta, V. Ramírez De Molina, P. Cejas, C. Ozu, C. Le, J. J. Sánchez, M. González-Barón, J. Koutcher, C. Cordón-Cardó, B. H. Bochner, J. C. Lacal, A. Ramírez De Molina

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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-α (ChoKα) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKα show antitumoral activity and are expected to be introduced soon in clinical trials. This study aims to assess whether ChoKα plays a role in the aggressiveness of bladder tumors and constitutes a new approach for bladder cancer treatment. We show here that ChoKα 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 ChoKα potentiate both tumor formation (P0.0001) and aggressiveness of the disease on different end points (P0.011). Accordingly, increased levels of ChoKα significantly reduce survival of mice with bladder cancer (P0.05). Finally, treatment with a ChoKα-specific inhibitor resulted in a significant inhibition of tumor growth (P0.02) and in a relevant increase in survival (P0.03).

Original languageEnglish (US)
Pages (from-to)2425-2435
Number of pages11
JournalOncogene
Volume28
Issue number26
DOIs
StatePublished - Jul 2 2009

Keywords

  • Bladder cancer
  • Choline kinase
  • Therapeutic target
  • Tumor promoter

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Hernando, E., Sarmentero-Estrada, J., Koppie, T., Belda-Iniesta, C., Ramírez De Molina, V., Cejas, P., Ozu, C., Le, C., Sánchez, J. J., González-Barón, M., Koutcher, J., Cordón-Cardó, C., Bochner, B. H., Lacal, J. C., & De Molina, A. R. (2009). A critical role for choline kinase-α in the aggressiveness of bladder carcinomas. Oncogene, 28(26), 2425-2435. https://doi.org/10.1038/onc.2009.91