As bowel cancer develops and progresses, there are significant changes in the organisation of the web of proteins forming the structure of bowel tissue. These changes cause tissue stiffness, which promotes growth of the cancer.
The research group studies an enzyme called TG2 which can cause inflammation in bowel cells, and once released from the cell can also link together these proteins. Bowel inflammation can lead to cancer, and they have seen that TG2 is abundant in colon cancer tissue, but how this affects the progression of disease is not known.
In this study the team will examine whether the protein linking caused by this enzyme changes the organization of the surrounding tissue, whether these changes alter how stiff the tissue becomes, and whether this makes the cancer more aggressive. This will open the door to new therapies that block TG2 and alter tissue stiffening.
The project will be managed by Dr Nicholas Peake, Senior Lecturer in Biomedical Sciences at Sheffield Hallam University and Professor Martin Knight, Professor of Mechanobiology and Director of Research at Queen Mary University of London.
Why target tissue stiffness to treat bowel cancer?
Inflammation is linked to cancer development. TG2 is known to have a role in inflammation and is also found in abundance in cancer tissue. However, how far TG2 contributes to the progression of cancer is as yet unknown. Increasing our knowledge of TG2 and its role in tissue stiffness will help us to better understand whether it is worth targeting the mechanistic process in potential new treatment regimes.
Long-term, this pilot project will support a larger study to investigate how colon cancer cells change how they respond to altered biomechanical properties of the surrounding tissue as the cancer spreads. This will be the first step in developing new drugs that target both cancer cells and the surrounding tissue.