Inflammation is linked to bowel cancer development. An enzyme called Transglutaminase-2 (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 not well known. Increasing our knowledge of TG2 and its role in the development of bowel cancer will help us to better understand whether it is worth targetting the enzyme and its mechanical processes in potential future treatment regimes.

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, led by Dr Nicholas Peake at Sheffield Hallam University, studies TG2.  Bowel & Cancer Research funding was secured to explore the role of TG2 in the progression of bowel cancer, in terms of both the promotion of inflammation and the mechanics of how bowel cancer grows within tissue, particularly the development of tissue stiffness and its role in helping bowel cancer to develop.

The results of the TG2 study are published in the journal Cancers

The team found that TG2 put the brakes on the growth of cancer cells in 3D models and in culture. They also observed the distinct mechanism by which the development of bowel cancer cells affected their environment by increasing the stiffness of surrounding tissue. This mechanical affect was also dampened by turning off TG2.

The same observations were made when looking at biopsied tissues from patients with bowel cancer, with TG2 associated with thickening collagen fibres and also poorer outcomes for patients in terms of disease recurrence following surgery and overall survival.

This study therefore successfully demonstrated a role for TG2 in outcomes for bowel cancer patients and as a target for future therapy discoveries.

The full findings can be accesses here: https://www.mdpi.com/2072-6694/11/5/701/htm.