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

2005; American Association for Cancer Research; Volume: 65; Issue: 13 Linguagem: Inglês

10.1158/0008-5472.can-04-4416

1538-7445

Ana Ramı́rez de Molina, David Gallego‐Ortega, Jacinto Sarmentero, Mónica Báñez-Coronel, Yolanda Martín-Cantalejo, Juan Carlos Lacal,

Microtubule and mitosis dynamics

Abstract 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.