Researchers discover potential new drug target in dividing cells

In collaboration with the Press Association

UK researchers studying how cells divide have discovered a potential new target for cancer drugs.

Their study published in the Journal of Cell Biology looks at the role played by a particular group of proteins in dividing cells.

When it divides in two, a cell separates the DNA chromosomes in its nucleus into two identical sets, to form the two new nuclei of the resulting cells.

The cell also produces a structure called the mitotic spindle, which makes sure that the chromosomes are divided equally between the two new cells. The spindle is made of bundles of long, thin proteins called microtubules.

These are the target of current chemotherapy drugs like paclitaxel. However, these drugs can have serious side effects as they target the microtubules in normal cells.

The scientists, based in Warwick and Leicester who were funded by Cancer Research UK, the Medical Research Council and the Royal Society, found that two proteins TACC3 and ch-TOG - act together during the formation of the spindle by working alongside a protein called clathrin.

Removing TACC3 from the cell meant the clathrin was no longer able to bind the microtubules together. This significantly weakened the microtubules and the mitotic spindle, causing the cells to die.

The researchers propose that blocking the action of this group of proteins could help target rapidly dividing cancer cells - something they now plan to study further.

Study author Professor Steve Royle said he hoped their future work would give the team a greater understanding of how this team of proteins can be used in a more clinical environment.

"If we could target the mitotic spindle proteins, rather than microtubules, we may be able to develop effective anti-cancer drugs with fewer side effects."

Commenting on the research, Professor Mark Petronczki - a cell division expert at Cancer Research UK's London Research Institute, who was not involved in the study - said that chemotherapy drugs that target dividing cells are a major part of treatment for many cancers.

"Many of these work by blocking the function of a structure known as the mitotic spindle. Unfortunately, this can have serious side effects for patients.

"The identification of the components of the inter-microtubule bridges provides researchers with an additional target against which to develop new drugs to attack dividing cancer cells, and to possibly avoid some of the side effects of existing treatments."

  • Image shows the mitotic spindle in a human cell, with the TACC3 protein in green, clathrin protein in red and DNA chromosomes in blue, courtesy of Dr Steve Royle/Warwick Uni.

Copyright Press Association 2013

References

  • Hood F.E., Williams S.J., Burgess S.G., Richards M.W., Roth D., Straube A., Pfuhl M., Bayliss R. & Royle S.J. Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding., The Journal of cell biology, PMID: