Study aims to prove that cell signals trigger cancer

Cells use an elaborate signalling system to control vital activities such as when to grow, divide and die

Cells use an elaborate signalling system to control vital activities such as when to grow, divide and die. This system, or another signalling system yet to be discovered, may trigger the onset of cancer, when cells grow out of control.

A research team from the University of Ulster, Coleraine, have embarked on a project to look at the signalling systems inside cells and whether they have a link with cancer. In particular, they are looking for protein fragments, peptides, involved in signalling.

"Everybody knows cells make large proteins and chop them up for signalling," explained Prof Stephen Downes, head of the Cancer and Ageing Research Group at Coleraine.

These peptide fragments support cell-to-cell communications, but Prof Downes is looking for a similar system that operates inside the cell.

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Prof Downes and Prof Chris Shaw, head of the Pharmaceutical Biotechnology Research Group at Colerain, will head the project. They received a grant from the Sir Henry Wellcome Commemorative Award scheme, a funding programme that encourages high-risk research where outcomes are unpredictable.

Most funding programmes require preliminary results to show a project has potential. "The trouble is if you have an original idea then you have no evidence for or against it," he added.

"It (the project) all started over a cup of coffee," Prof Downes said. The two researchers were chatting about Prof Shaw's work on peptide signalling between cells.

"We thought, for all we knew when you break down the big proteins, the small pieces of peptide act as signals inside the cell," Prof Downes said.

"We know that when the signalling system inside cells which controls cell growth goes wrong it causes cancer," Prof Downes explained. "The problem is that we only partly understand how those internal signalling systems work."

The search is now on for peptides inside the cell that may be signalling cell division and DNA replication. "We are looking into a haystack for a needle which may or may not be there," Prof Downes said. "If they do exist then we will have information for a new signalling system relevant to cancer which has not previously been known to exist."

Their interest focuses on the fact that the controlling mechanism inside the cell goes wrong when cancer occurs. It may be that a missing or mutated peptide may be the initial trigger that leads to the unregulated cell growth of cancer. "And if we can find out what goes wrong, then we can hope to find out how to put it right," Prof Downes added.

The research team will use established techniques including mass spectrometry in their search for peptide signals inside the cell. They will study the large proteins formed in the cell and will then catalogue the resultant breakdown fragments.

Individual peptides will be tracked to see where they go and what biochemical affect they have in the cell. If the researchers find something of interest, they will synthesise the peptide and introduce it into cultured cells in vitro to see whether it has an impact on the cell cycle.

Given the well-established role of peptides in cell-to-cell signalling, it seemed surprising that a similar system inside the cell had not been sought before.

Prof Downes said scientists were so busy looking at the big proteins and trying to understand what they did that there had not been time to look at what the peptides were doing inside the cell. UU Coleraine hopes to correct this situation.