This project aims to understand how a specific mutation in a gene called gp130 causes stomach inflammation (gastritis) and cancer. These results can also increase our understanding of how inflammation promotes other types of cancer (e.g. colon).
It is established that 25% of all cancers, including stomach, prostate, colon and liver, are caused by infection and inflammation. Among these, stomach (gastric) cancer is the second most common cause of cancer-related deaths worldwide.
A strong link has been established between gastric cancer and chronic gastric inflammation (gastritis) triggered by infection with Helicobacter pylori (H. pylori) bacteria. Despite these observations, it is still unknown how such infections trigger chronic gastritis and gastric cancer in some people, but not others.
Our laboratory has discovered a specific mutation in a gene called gp130 that results in the formation of gastritis and gastric cancer in mice. Furthermore, we have recently identified that the gp130 mutation in gastric cells increases the production of proteins on the cell-surface that are important for recognizing bacteria, including H. pylori, and triggering inflammatory responses.
Thus, we believe that the increased production of these proteins will lead to their increased activation by bacteria, and ultimately bacterial-driven chronic inflammation. We are now aiming to understand exactly how this mutation results in chronic inflammation and the subsequent uncontrolled growth of gastric cells.