Featured Research

from universities, journals, and other organizations

Bacterial gut biome may guide colon cancer progression

Date:
April 4, 2014
Source:
The Wistar Institute
Summary:
Gut bacteria can change the microenvironment in a way that promotes the growth and spread of tumors, research demonstrates. The results suggest that bacterial virulence proteins may suppress DNA repair proteins within the epithelial cells that line the colon. "There is a drastic, unmet need to look at new ways to define exactly how colon cancer forms in the gut and what triggers its progression into a lethal form," said the lead researcher. "We suggest that some bacterial proteins can promote genetic changes that create conditions in the gut that would favor the progression of colon cancer."

Colorectal cancer develops in what is probably the most complex environment in the human body, a place where human cells cohabitate with a colony of approximately 10 trillion bacteria, most of which are unknown. At the 2014 American Association for Cancer Research Annual Meeting in San Diego, researchers from The Wistar Institute will present findings that suggest the colon "microbiome" of gut bacteria can change the tumor microenvironment in a way that promotes the growth and spread of tumors.

Their results suggest that bacterial virulence proteins may suppress DNA repair proteins within the epithelial cells that line the colon. The research opens the possibility of modifying colon cancer risk by altering the population makeup of bacteria in the intestines of people at risk due to genetics or environmental exposure.

"There is a drastic, unmet need to look at new ways to define exactly how colon cancer forms in the gut and what triggers its progression into a lethal form," said Frank Rauscher, III, Ph.D., a professor in The Wistar Institute Cancer Center. "We suggest that some bacterial proteins can promote genetic changes that create conditions in the gut that would favor the progression of colon cancer."

While colorectal cancer incidence rates have declined, likely due to more widespread screening, survival rates have not. According to the American Cancer Society, about 50,000 Americans will die from colorectal cancer this year. "While our understanding of the gene mutations involved in colon cancer has improved, this has not lead to the promised increases in overall survival," Rauscher said.

Intestinal bacteria typically provide many benefits to their human hosts, aiding in digestion and crowding out more directly pathogenic bacteria. However, both "friendly" commensal bacteria and infective, pathogenic bacteria have been shown to actively reduce inflammation, an important tool used by the human innate immune system to promote healing and prevent the spread of infection.

In these studies, Rauscher and his colleagues injected anti-inflammatory proteins produced by EPEC (Enteropathogenic Escherichia coli) bacteria into colon epithelial cells. One of these proteins, NLEE, is an enzyme that targets TAB2, a human scaffolding protein involved in the transduction of chemical signals in the NF-κB pathway. Targeting TAB2 results in the inactivation of numerous inflammatory activities in the gut.

Rauscher and colleagues looked for other human proteins that could be targeted by NLEE. Remarkably, they found that NLEE also has the capability of shutting off a protein, ZRANB3 involved in DNA repair. If bacterially infected colon cells can no longer repair damage to their DNA, mutations will accumulate, which will promote cancer growth.

In addition, along with collaborators in the laboratory of Feng Shao, Ph.D., at the National Institute of Biological Sciences in Beijing, China, they demonstrated that NLEE proteins attack TAB2 and ZRANB3 by methlylating these proteins -- essentially adding a single methyl molecule -- which unfolds the target proteins. NLEE appear to specifically attack a structure on TAB2 and ZRANB3 known as a "zinc finger," which is a common structural motif used in many other proteins. When the researchers determined the structure of NLEE, they found a deep cleft on the protein specific to a certain zinc finger pattern. A survey of EPEC-infected colon cells showed that this zinc finger pattern was common to at least three DNA repair enzymes, suggesting that NLEE has the capability of having widespread influence on mechanisms in the colon that typically prevent cancer growth.

"Our results suggest that some infective intestinal bacteria, which normally can simply cause gastric distress, have the capability of inducing genetic changes (by limiting repair) in our intestinal cells which could lead to tumor development," Rauscher explained. "It is possible that limiting the amount of this bacteria in our gut may protect us from the genetic changes which accumulate in our intestinal cells over time and lead to cancer development."

According to Rauscher, this is a new way to look at the microenvironment in the gut as an incubator for colon cancer, depending upon which type and species of bacteria are resident and potentially infectious in our large intestines. Rauscher and his collaborators are currently embarking on a project to further test their hypothesis.


Story Source:

The above story is based on materials provided by The Wistar Institute. Note: Materials may be edited for content and length.


Cite This Page:

The Wistar Institute. "Bacterial gut biome may guide colon cancer progression." ScienceDaily. ScienceDaily, 4 April 2014. <www.sciencedaily.com/releases/2014/04/140404140407.htm>.
The Wistar Institute. (2014, April 4). Bacterial gut biome may guide colon cancer progression. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2014/04/140404140407.htm
The Wistar Institute. "Bacterial gut biome may guide colon cancer progression." ScienceDaily. www.sciencedaily.com/releases/2014/04/140404140407.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins