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Cancer Res. 2005 Jul 1;65(13):5647-53.

Choline kinase is a novel oncogene that potentiates RhoA-induced carcinogenesis.

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  • 1Unidad de Oncología Translacional, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Cientificas-UAM, Spain.

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.

PMID:
15994937
[PubMed - indexed for MEDLINE]
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