Link between, bacteria, cancer explored with funding from American Cancer Society

The role of bacteria in the development of colorectal cancer is coming under scrutiny at the University of Rochester Medical Center, thanks to an $840,000 research award from the American Cancer Society.

Jun Sun, Ph.D., assistant professor in the Gastroenterology and Hepatology Division of the Department of Medicine, is using the funds to put together a team of scientists exploring links between intestinal bacteria and colon cancer.

Sun has quickly established herself as a leader in this area, demonstrating that bacteria often found in the human intestine affect molecular signals in the body known to contribute to colorectal cancer, a disease that, according to ACS estimates, killed about 50,000 people in the United States last year.

While most scientists believe that bacteria play an important role in the development of colon cancer, how they might do so directly in people is not known. Sun is one of very few researchers in the world who have actually linked bacterial proteins to known cancer-causing signals in people.

Part of Sun's challenge is to cut through the complexity and murk of the environment of the human colon. The intestines and stomach teem with more than 500 species of bacteria which comprise more than 100 trillion microbial cells - more than 10 times the total number of human cells in the entire human body.

Sun is honing in on a protein known as AvrA, which is found in some types of bacteria, such as Salmonella. The protein is injected into human cells by a syringe-like system that allows bacteria to shoot toxins and proteins into cells just seconds after encountering them in the intestines. AvrA is especially adept at functioning in low-acid locales like the gut and bears close resemblance to a protein active in the bug that caused the Black Plague.

In one set of studies, Sun's team explores the short-term effects of AvrA. Her team has found that the protein is one reason why Salmonella is so deadly. AvrA reduces the body's inflammatory response, helping bacteria avoid the body's immune system in the early stages of infection and giving the bacteria time to grow and develop into a more dangerous threat.

In the project funded by ACS, Sun is exploring the long-term effects of AvrA. She has found that AvrA affects the molecule beta-catenin, a powerful molecule that is known to promote colon cancer in people.

"It's possible that activation of beta-catenin by AvrA over the long term, for instance many years, could promote cancer," said Sun.

Her early studies have shown that the more active that AvrA is in the cells lining the intestine, the more likely colon cancer is to develop, perhaps because of the protein's effect on beta-catenin.

"It may be that bacteria equipped with AvrA pose an important risk factor for developing colon cancer. Monitoring the bacteria may help us to know who is at greater risk for the disease, and maybe it will be possible to manipulate the protein to help prevent colon cancer," said Sun.

Sun is a graduate of Wuhan University and the Institute of Toxicology and Pharmacology in China. She served as a visiting scholar at the National Cancer Institute and a researcher at Emory University and the University of Chicago before joining the University of Rochester Medical Center in 2007.

This May, Sun will give a plenary lecture on the topic at the annual meeting of the American Gastroenterological Assn., marking the second time in three years that she has been invited to present her findings to her colleagues from around the world. She also has $650,000 in funding from the National Institute of Diabetes and Digestive and Kidney Diseases to explore bacteria's role in inflammation in the intestine.

Sun received the ACS funds this past weekend at a celebration by volunteers for the ACS Relay for Life, an overnight event where individuals and teams camp out, picnic, dance and take turns walking or running around a track to raise funds to fight cancer. According to ACS, Relay For Life represents hope in that those lost to cancer will not be forgotten, that those who face cancer will be supported, and that one day, cancer will be eliminated.

Since 1994, the American Cancer Society's Research and Training Program has funded nearly $15 million in awards to researchers at the University of Rochester and at the University's James P. Wilmot Cancer Center.

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