Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: Implications in cancer therapy

Choline kinase alpha (ChoK alpha) is an enzyme involved in the metabolism of phospholipids recently found to play a relevant role in the regulation of cell proliferation, oncogenic transformation and human carcinogenesis. In addition, this novel oncogene has been recently defined as a prognostic factor in human cancer, and as a promising target for therapy since its specific inhibitors display efficient antitumoral activity in vivo. However, the mechanism by which this enzyme is involved in the regulation of these processes is not yet understood. Using differential microarray analysis, we identify target genes that provide the basis for the understanding of the molecular mechanism for the regulation of cell proliferation and transformation mediated by over-expression of the human ChoK alpha. These results fully support a critical role of this enzyme in the regulation of the G1 double right arrow S transition at different levels, and its relevant role in human carcinogenesis. The molecular basis to understand the connection between phospholipids metabolism and cell cycle regulation through choline kinase is reported. (C) 2008 Elsevier Ltd. All rights reserved.