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Choline Kinase Is a Novel Oncogene that Potentiates RhoA-Induced Carcinogenesis

¹ Unidad de Oncología Translacional, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-UAM and ² Dpto Química y Materiales, Universidad Europea de Madrid, Villaviciosa de Odón, Madrid, Spain

Requests for reprints: Juan Carlos Lacal, Instituto de Investigaciones Biomédicas, Molecular and Cellular Biology of Cancer, Arturo Duperier 4, Madrid, Spain, 28029. Phone: 34-91-585-4607; Fax: 34-91-585-4606 / 585-4587; E-mail: jclacal{at}iib.uam.es.

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.