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Background

To date, there are few reports on gene products contributing to colon cancer progression.

Methods

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.

Results

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.

Conclusions

CLCN4 is a novel driver of colon cancer progression."xsd:string
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http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Nakamura T."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Yamamoto M."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Lin S.Y."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Ishiguro T."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Avila H."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/author"Boyd D.D."xsd:string
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http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/name"Br J Cancer"xsd:string
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http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/title"Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases."xsd:string
http://purl.uniprot.org/citations/20087350http://purl.uniprot.org/core/volume"102"xsd:string
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