"Scientists at St. Jude Childrens Research Hospital have discovered how an immune system protein called AIM Absent in Melanoma  plays a role in determining the aggressiveness of colon cancer. They found that AIM deficiency causes uncontrolled proliferation of intestinal cells. Surprisingly they also discovered that AIM influences the microbiota  the population of gut bacteria  apparently fostering the proliferation of good bacteria that can protect against colon cancer.  The team led by ThirumalaDevi Kanneganti Ph.D. a member of the St. Jude Department of Immunology published their findings in a recent issue of the journal Cell. She said that the findings could have important applications for prevention prognosis and treatment. Since reduced AIM activity in colorectal cancer patients is associated with poor survival it might be useful to detect the level of AIM expression in polyps taken from colonoscopy and use this as one of the biomarkers for prognosis Kanneganti said. Kanneganti and her team believe that it might be possible to prevent the disease or reduce its risk by treating susceptible people to increase AIM activity and give them healthy donor bacteria. In people who already have colorectal cancer therapies that boost the expression of AIM such as interferons might reduce tumor progression. Also transferring healthy microbiota or a group of good bacteria to patients with colorectal cancer at the early stage of disease may prolong survival Kanneganti said. Cancer researchers had known that mutations in AIM were frequently found in patients with colorectal cancers. And a study by other researchers had found that more than half of small bowel tumors had AIM mutations. However AIMs established function in the cell was not in the machinery of cancer said one of the papers first authors Si Ming Man Ph.D. a postdoctoral fellow in Kannegantis laboratory. Rather he said AIM was known to work in the immune system to detect invading bacteria and viruses and help alert the immune system to battle them. When we found that the intestine expressed high levels of AIM we hypothesized that this gene may also play a role in regulating gut health Man said. This was how we became interested in AIM and colorectal cancer. In their experiments with mice the scientists used chemicals to trigger the process mimicking the development of colorectal cancer. They found that the mice showed drastically reduced AIM function confirming the finding in humans with the cancer. They also found that mice genetically altered to have reduced AIM function when treated with the chemicals showed significantly more tumors than normal mice. The scientists studies also showed that AIM played a role independent of its immune role in suppressing abnormal expansion of intestinal stem cell populations. Conversely malfunction of AIM unleashes abnormal stem cell proliferation. Stem cells are immature cells that differentiate into adult cells such as intestinal cells. These cells continuously proliferate to replace old and dying cells in the intestine. Many previous studies have indicated that AIM contributes to the immune system by acting as a pathogen sensor Man said. However our work is the first to identify AIMs role in controlling proliferation of intestinal stem cells. This work is truly exciting to us because we have found a new role for AIM in regulating colorectal cancer and it does so by inhibiting excessive proliferation of stem cells in the large intestine. The researchers also pinpointed the specific cellular machinery regulated by AIM. They decided to explore whether AIMs protective role might involve gut bacteria based on studies from Kannegantis lab and others indicating that microbial sensors similar to AIM contributed to healthy gut microbiota. Indeed the comparison of gut bacteria in normal and AIMdeficient mice showed a different microbial landscape in the two types of mice. To test whether gut bacteria might influence the progression of colon cancer the researchers housed normal and AIMdeficient mice together to enable the exchange of gut bacteria. The scientists found a striking reduction in colon tumors in the AIMdeficient mice and an increase in tumors in the normal mice. What this might suggest is that transfer of some of the good microbiota from wildtype mice to replace the bad microbiota from mice lacking AIM offers increased protection against colorectal cancer Man said. We believe that this finding has important clinical relevance because we can potentially prevent or decelerate the progression of colorectal cancer in humans especially in those who have mutations in the AIM gene by simply giving them good microbiota. We have only scratched the surface of the role of AIM in controlling stem cell proliferation and the maintenance of a healthy gut microbiota Kanneganti said. How exactly AIM does both of these functions is an exciting research area to pursue.  The papers other authors are Qifan Zhu Liqin Zhu Zhiping Liu Rajendra Karki Ankit Malik Deepika Sharma Liyuan Li R.K. Subbarao Malireddi Prajwal Gurung Geoffrey Neale Scott Olsen Robert Carter Daniel McGoldrick Gang Wu David Finkelstein Peter Vogel and Richard Gilbertson all of St. Jude. The research was funded in part by grants AR CA AI from the National Institutes of Health and ALSAC. Contact Carrie Strehlau carrie.strehlaustjude.org mailtocarrie.strehlaustjude.org Desk  or Cell   Frannie Marmorstein frannie.marmorsteinstjude.org mailtofrannie.marmorsteinstjude.org Desk  or Cell   About St. Jude Childrens Research Hospital St. Jude Childrens Research Hospital is leading the way the world understands treats and defeats childhood cancer and other lifethreatening diseases. It is the only National Cancer Institutedesignated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from  percent to  percent since the hospital opened more than  years ago. St. Jude is working to increase the overall survival rate for childhood cancer to  percent in the next decade. St. Jude freely shares the breakthroughs it makes and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment travel housing and food  because all a family should worry about is helping their child live. To learn more visit stjude.org http or follow St. Jude at stjuderesearch http"