Chronic inflammation increases the risk of developing cancer. For example, patients
with severe and prolonged inflammatory bowel disease, particularly ulcerative colitis, have a
significantly higher risk of developing colorectal cancer. Serine proteases coordinating the coagulation
cascade and immune cell proteases play important roles in regulating the inflammatory
response through their actions on protease-activated receptors (PAR). PARs and their activating
proteases have also been implicated in many cancers, including CRC. Importantly, the actions of
proteases could be important for mediating the transition from chronic inflammation to cancer.
PAR activation has been shown to have pro-tumourigenic effects including the production of
matrix metalloproteinases that can promote tumour cell growth and metastasis, and transactivation
of the epidermal growth factor receptor, which is a main target for cancer treatment. Additionally, PAR activation can also result in
increased expression of cyclooxygenase (COX)-2, an important enzyme mediating inflammation, resolution, and cancer progression. In
this review, we will highlight our current knowledge about the effects of proteases and their receptors on intestinal inflammation and
cancer, and explore the potential role of PAR-induced COX-2 on colitis-associated cancer.
Keywords: colitis-associated cancer, colorectal cancer, cyclooxygenase-2, inflammatory bowel disease, protease-activated receptors, serine
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