Choline Kinase Is a Novel Oncogene that Potentiates RhoA-Induced Carcinogenesis
Open Access
- 1 July 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (13), 5647-5653
- https://doi.org/10.1158/0008-5472.can-04-4416
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.Keywords
This publication has 30 references indexed in Scilit:
- Rho GTPase expression in tumourigenesis: Evidence for a significant linkBioEssays, 2005
- Rho GTPases in human cancer: an unresolved link to upstream and downstream transcriptional regulationBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2004
- Structure and function of choline kinase isoforms in mammalian cellsProgress in Lipid Research, 2004
- Inhibition of choline kinase as a specific cytotoxic strategy in oncogene-transformed cellsOncogene, 2003
- ROCK and Nuclear Factor-κB–dependent Activation of Cyclooxygenase-2 by Rho GTPases: Effects on Tumor Growth and Therapeutic ConsequencesMolecular Biology of the Cell, 2003
- RhoA and ROCK Promote Migration by Limiting Membrane ProtrusionsJournal of Biological Chemistry, 2003
- Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancersBiochemical and Biophysical Research Communications, 2002
- Regulation of gene expression by the small GTPase Rho through the ERK6 (p38γ) MAP kinase pathwayGenes & Development, 2001
- Rho proteins induce metastatic properties in vivoOncogene, 1997
- Phospholipid metabolites as indicators of cancer cell functionNMR in Biomedicine, 1992