Choline Kinase—More Than a Cancer Therapy Target?

RESEARCH HIGHLIGHTS Nature Reviews Rheumatology 10, 699 (2014); published online 21 October 2014; doi:10.1038/nrrheum.2014.180

RHEUMATOID ARTHRITIS Choline kinase—more than a cancer therapy target?

“Blocking choline kinase suppressed the By immunohistochemistry, western blot Fibroblast-like synoviocyte in RA 1 aggressive behavior of fibroblast-like and H magnetic resonance spectroscopy, ATP + choline synoviocytes in rheumatoid arthritis the researchers showed choline kinase α Mg2+ Choline and was highly effective in a preclinical is highly expressed in the synovium of kinase model of arthritis,” says Monica Guma, patients with RA, particularly in the Phosphocholine + ADP corresponding author of a study published intimal layer, and also in ex vivo cultured in Annals of the Rheumatic Diseases. fibroblast-like synoviocytes. Expression

NPG Phosphatidylcholine Choline kinase is a phosphotransferase of the enzyme was shown to be induced enzyme that catalyzes the conversion of by inflammatory stimuli, including TNF, In reference to ongoing and planned choline to phosphocholine, a first step in IL-1 and platelet-derived growth factor, work, the lead researcher of the study, the biosynthesis of phosphatidylcholine but not lipopolysaccharide. Gary Firestein, comments, “We would (see figure). Phosphatidylcholine The researchers found that mitogen- like to determine the suitability of choline metabolism affects cell proliferation, activated protein kinase and PI3K/Akt metabolites or other metabolites as migration and signalling, and through signalling by fibroblast-like synoviocytes biomarkers of fibroblast-like synoviocyte these mechanisms is thought to be an could be reduced with a choline activation and joint damage in patients important regulator of tumorigenesis. kinase inhibitor (MN58b). These data with RA. If successful, our studies could In explanation of why her group began complement knowledge of the tumour cell translate into important diagnostic and studying metabolic abnormalities in RA, biology and contribute to understanding prognostic tests.” Guma says, “Targeting the metabolome of the mouse modelling data, that is, Nicholas J. Bernard in cancer is now emerging as a potential administration of MN58b reduced clinical therapeutic approach. The joint in RA has scores of established disease severity in the many characteristics of tumors, including K/BxN serum transfer mouse model of Original article Guma, M. et al. Choline kinase inhibition hypoxia and high levels of oxygen radicals, inflammatory arthritis, when compared in rheumatoid arthritis. Ann. Rheum. Dis. doi:10.1136/ annrheumdis-2014-205696 nitric oxide and cytokines.” with vehicle-treated control mice.