Researchers Turn Tumor Suppressor into Anti-Cancer Target

Researchers show how in mice the elimination of the Cdh1 protein —a sub-unit of the APC/C complex, involved in the control of cell division—prevents cellular proliferation of rapidly dividing cells.

Researchers show how in mice the elimination of the Cdh1 protein —a sub-unit of the APC/C complex, involved in the control of cell division—prevents cellular proliferation of rapidly dividing cells.

The researchers are from laboratory of Marcos Malumbres, who is head of the Spanish National Cancer Research Centre's (CNIO) Cell Division & Cancer Group, working alongside Isabel Fariñas' team from the University of Valencia.

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Malumbres's group had previously discovered that the inactivation of another APC/C protein, Cdc20, prevented cell division. These results caught the attention of pharmaceutical companies, who are already developing the first inhibitors from the complex. These molecules have caused controversy due to the possible side effects of blocking Cdh1, which is considered a tumour suppressor.

Manuel Eguren has analysed the biological consequences of Cdh1 elimination in rapidly dividing cells, as part of his doctoral research project in Malumbres's group; he focused on progenitors from the nervous system during embryonic development in mice.

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Via a detailed biochemical and cell study, researchers have discovered that the absence of Cdh1 causes DNA damage in cells. This defect causes cell death and leads to alterations in the development of the nervous system such as hydrocephalus, characterised by abnormal accumulation of fluid on the brain.

"Our results solve the controversy about the possible side effects of APC/C inhibitors", says Malumbres, adding that: "we have shown in vivo that their elimination leads to the death of rapidly dividing cells".