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- W2002893263 abstract "To date, there are few reports on gene products contributing to colon cancer progression. We used a gene trap comprised of an enhanced retroviral mutagen (ERM) cassette that includes a tetracycline-responsive promoter upstream of a haemagglutinin (HA) tag and a splice donor site. Integration of the ERM within an endogenous gene yields a tetracycline-regulated HA-tagged transcript. We transduced RKO colon cancer cells expressing a tetracycline trans-activator-off with the ERM-encoding retrovirus and screened for enhanced migration. One clone showed fivefold enhanced migration with tetracycline withdrawal. Rapid amplification of cDNA ends identified the trapped gene as the chloride channel 4 (CLCN4) exchanger. Stable expression of a CLCN4 cDNA enhanced motility, whereas cells knocked down or null for this transcript showed reduced migration/invasion. CLCN4-overexpressing RKO colon cancer cells were more resistant than controls to proton load-induced cytotoxicity, consistent with the H+-extruding function of this antiporter. Intra-splenic delivery of RKO-CLCN4 transfectants, but not controls, yielded liver metastases, and transcript levels were higher in colon cancer metastases to the liver when compared with primary tumours. CLCN4 is a novel driver of colon cancer progression." @default.
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- W2002893263 date "2010-01-19" @default.
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- W2002893263 title "Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases" @default.
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- W2002893263 doi "https://doi.org/10.1038/sj.bjc.6605536" @default.
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