Stomach cancer culprit is in the immune system
A study on how genes of the immune system influence the development of gastric (stomach) cancer has identified a key contributor, offering the potential for better prognosis and treatment of this deadly disease.
AIM2 is part of the innate immune system, the body’s first line of defence against invading pathogens and tissue injury, and is already known to be linked with several inflammatory and autoimmune diseases. However, its role in cancer is not well investigated.
Dr Dawson said there is a well-established link between chronic gastric inflammation (gastritis) and gastric cancer, but regulators of innate immunity that can drive this cancer are less well understood, until now.
“We found that high levels of AIM2 drives tumour formation in the stomach. Interestingly, the outcome that high AIM2 had on the stomach was found to be through increasing cancer cell movement and not through its more well-known function in inflammation,” Dr Dawson said.
“This change in cell movement was dependant on the interaction of the AIM2 protein with another protein, called EB1, which we also show is linked with poor prognosis of gastric cancer patients.”
“You can think of a cell as a finely tuned orchestra of many different instruments; playing together in harmony and taking cues from each in order to make music. In our situation, the AIM2 instrument was playing too loud, which disrupted surrounding instruments and the song the orchestra was playing. In the same way the song is ruined as it becomes too chaotic, the cell becomes cancerous.”
Gastric or stomach cancer is the third most lethal cancer worldwide, with a 5-year survival rate of less than 30%.
Identifying the role of AIM2 and EB1 in the development of this cancer could give doctors a clearer picture of a patient’s survival outcome and the ability to offer more personalised treatment options.
“We now have the ability to better predict the prognosis of people diagnosed with gastric cancer through measuring levels of AIM2 and EB1,” Dr Dawson said. “Furthermore, with a better understanding of the mechanism behind these genes, we have more scope to selectively target them to develop novel therapies for gastric cancer.”
This work was funded by the National Health and Medical Research Council (NHMRC). Support was also provided by Australian Postgraduate Awards, an NHMRC Early Career Fellowship and an NHMRC Senior Medical Research Fellowship.
You can see the paper STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis in the BMJ journal, Gut.
Hudson Institute communications
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