Cell Mesh Structure Discovery Sheds Light On Cancer Development

A cell structure called ‘the mesh’ has been discovered which helps to hold together cells. The discovery changes scientists understanding of the cell’s internal scaffolding and could help us better understand why some cancers develop.

Researchers at the University of Warwick Medical School made the discovery accidentally, while looking at gaps between microtubules, which are part of the cells’ internal scaffolding. In dividing cells, these gaps are incredibly small at just 25 nanometres wide, 3,000 times thinner than a human hair.

Team leader Dr Stephen Royle, senior Cancer Research UK Fellow at the division of biomedical cell biology at Warwick Medical School, said:

“As a cell biologist you dream of finding a new structure in cells but it’s so unlikely. Scientists have been looking at cells since the 17th Century and so to find something that no-one has seen before is amazing.”

One of Dr Royle’s PhD students was examining structures called mitotic spindles in dividing cells using a technique called tomography which is like a hospital CAT scan but on a much smaller scale. This meant that they could see the structure which they later named the mesh.

Mitotic Spindles

Mitotic spindles are the cell’s way of making sure that when they divide each new cell has a complete genome.

The spindles are made of microtubules and the mesh holds the microtubules together, providing support. While “inter-microtubule bridges” in the mitotic spindle had been seen before, the researchers were the first to view the mesh.

Dr Royle said:

“We had been looking in 2D and this gave the impression that ‘bridges’ linked microtubules together. This had been known since the 1970s. All of a sudden, tilting the fibre in 3D showed us that the bridges were not single struts at all but a web-like structure linking all the microtubules together.”

The discovery will have impacts on research into cancerous cells.

A cell needs to share chromosomes accurately when it divides otherwise the two new cells can end up with the wrong number of chromosomes. This is called aneuploidy and this has been linked to a range of tumours in different body organs.

Trouble Sharing Chromosomes

The mitotic spindle is responsible for sharing the chromosomes and the researchers believe that the mesh is needed to give structural support. Too little support from the mesh and the spindle will be too weak to work properly, however too much support will result in it being unable to correct mistakes.

It was found that one of the proteins that make up the mesh, TACC3, is over-produced in certain cancers. When this situation was mimicked in the lab, the mesh and microtubules were altered and cells had trouble sharing chromosomes during division.

Dr Emma Smith, senior science communications officer at Cancer Research UK, said:

“Problems in cell division are common in cancer – cells frequently end up with the wrong number of chromosomes. This early research provides the first glimpse of a structure that helps share out a cell’s chromosomes correctly when it divides, and it might be a crucial insight into why this process becomes faulty in cancer and whether drugs could be developed to stop it from happening.”

Faye M Nixon, Cristina Gutiérrez-Caballero, Fiona E Hood, Daniel G Booth, Ian A Prior, Stephen J Royle
The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle
eLife 2015;4:e07635 DOI: http://dx.doi.org/10.7554/eLife.07635

Photo: A 3-D view of the mesh: microtubules (green tubes) of the mitotic spindle are held together by a yellow network, the mesh. Credit: Warwick Medical School

Video: Tomogram of a K-fiber. The mesh (yellow) is shown by manual rendering and by automated rendering. MTs (green) were rendered by hand. All segmentation was smoothed in Amira. Credit: Warwick Medical School