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Cowboy lasso key to cancer treatment

Scientists have compared a protein vital for passing on an accurate copy of the genome from mother to daughter cells to a cowboy’s lasso.

 

The molecule catches chromosomes and ties them to a structure assembled during cell division. Once they have been neatly tied up, the chromosomes await the end of replication to be equally distributed between the two daughter cells. But if the lasso doesn’t catch them, chromosomes end up being randomly scattered, with potentially disastrous genetic effects.

The researchers hope that the findings open up new avenues of research to reduce the toxicity of chemotherapy in the treatment of cancer.

“We’ve been studying a molecule called Ndc80,” said Andrea Musacchio, principal author of the study, and head of a research group at the new center for biomedical research, created by the joint efforts of the IFOM-IEO in Italy. “This protein is a key player necessary for the correct distribution of genetic inheritance. Ndc80 could potentially be used as a target for new drugs that would have fewer toxic side-effects than current drugs which mainly act as inhibitors of cell replication.”

Traditional chemotherapy targets often have other cellular functions. Ndc80, on the other hand, performs its job only during mitosis so by blocking its action the only cells affected would be the dividing ones. Musacchio and his colleagues are already testing a number of substances that might be able to block the action of Ndc80.

Musacchio said: “We had hypothesised that Ndc80 was only active during cell division, which is why we thought it might be an interesting target to study. And our results proved us right. We discovered that Ndc80 acts as a kind of molecular lasso that tethers chromosomes to the mitotic spindle, a molecular structure that only forms during mitosis. Ndc80 straps chromosomes firmly onto the spindle until the dividing cells separate; after this stage, it is of no more use to the cell. So, if we interfere with Ndc80, we can significantly reduce the so-called ‘toxicity window’.”

IFOM-IEO campus hosts the laboratories of the FIRC Institute of Molecular Oncology Foundation – IFOM – and of the European Institute of Oncology – IEO. The findings have just been published in the journal, Cell.

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