Choline kinase is a novel oncogene that potentiates RhoA-induced carcinogenesis.
Choline kinase is overexpressed in human breast, lung, colorectal, and prostate tumors, a finding that suggests the involvement of this enzyme in carcinogenesis. Here we show that overexpression of choline kinase induce oncogenic transformation of human embryo kidney fibroblasts and canine epithelial Madin-Darby canine kidney cells. Choline kinase lays downstream of RhoA signaling and is activated through ROCK kinase, one of the best-characterized RhoA effectors. In keeping with this, coexpression of RhoA and choline kinase potentiates both anchorage independent growth and tumorigenesis. Finally, choline kinase-mediated transformation is sensitive to MN58b, a well-characterized specific choline kinase inhibitor. These results provide the definitive evidence that choline kinase has oncogenic properties and that choline kinase inhibition constitutes a novel valid antitumor strategy.
Unidad de Oncología Translacional, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-UAM, Spain.
Ana
A
Ramírez de Molina
David
D
Gallego-Ortega
Jacinto
J
Sarmentero
Mónica
M
Bañez-Coronel
Yolanda
Y
Martín-Cantalejo
Juan Carlos
JC
Lacal
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002797:Choline Kinase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009857:Oncogenes; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D002797:Choline Kinase; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein