Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: implications in cancer therapy.
Choline kinase alpha (ChoKalpha) 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 ChoKalpha. These results fully support a critical role of this enzyme in the regulation of the G1-->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.
Ramírez de Molina
Ana
A
Translational Oncology Unit CSIC-UAM-La Paz, Centro Nacional de Biotecnología (CNB), Darwin 3, 28049 Madrid, Spain.
Gallego-Ortega
David
D
Sarmentero-Estrada
Jacinto
J
Lagares
David
D
Gómez Del Pulgar
Teresa
T
Bandrés
Eva
E
García-Foncillas
Jesús
J
Lacal
Juan Carlos
JC
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002417:Cattle; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002797:Choline Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010743:Phospholipids / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D010743:Phospholipids; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C517212:CHKA protein, human; D002797:Choline Kinase