Scientists from St.Jude Children’s Hospital have identified one gene that expresses in immune system plays important role in determining the invasiveness of colon cancer. Their study was published in Cell and may play vital role in the prevention, diagnosis, and treatment of colon cancer.

Colorectal cancer is a leading cause of cancer-related deaths, with 160,000 cases being diagnosed annually in the USA. Mutations in the gene encoding AIM2 are frequently identified in patients with colorectal cancer. A previous study has shown that more than 50% of tumors from patients with small bowel cancer have frameshift mutations in the gene encoding AIM2. Further genetic evidence has shown that missense mutations are targeted to coding regions of the gene encoding AIM2 in colon cancer tissues and cell lines. AIM2 is a cytosolic double-stranded DNA receptor that contributes to the host defense against bacterial and viral pathogens.

In this study, researchers found that AIM2-deficient mice developed more tumors in the colon following azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced colitis-associated tumorigenesis. Unlike its role in the host defense against infection, AIM2 protected against tumorigenesis by controlling intestinal epithelial cell proliferation via a mechanism independent of inflammasomes and inflammatory mediators. Upon deregulated Wnt signaling, AIM2 suppressed expansion of tumor-initiating intestinal stem cells lining the base of the crypt.

Remarkbaly, reciprocal exchange of the gut microbiota between healthy WT mice and Aim2^-/- mice reduced the susceptibility of Aim2^-/- mice to colorectal tumorigenesis. These findings revealed a role for AIM2 and its synergy with gut microbiota in the development of colorectal cancer.