Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases.
Br J Cancer
; 102(4): 774-82, 2010 Feb 16.
Article
em En
| MEDLINE
| ID: mdl-20087350
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma
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Movimento Celular
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Neoplasias do Colo
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Canais de Cloreto
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article