Featured Research

from universities, journals, and other organizations

Cancer-causing bacterium targets tumor-suppressor protein

Date:
August 2, 2010
Source:
University of Illinois at Urbana-Champaign
Summary:
Researchers have discovered a mechanism by which Helicobacter pylori, the only known cancer-causing bacterium, disables a tumor suppressor protein in host cells. Their study reports the discovery of a previously unknown mechanism linking H. pylori infection and stomach cancer, the second leading cause of cancer deaths worldwide.

A protein produced by some strains of H. pylori interacts with a host tumor suppressor protein. This leads to degradation of the tumor suppressor protein, researchers found.
Credit: Yutaka Tsutsumi, M.D. Professor Department of Pathology Fujita Health University School of Medicine via Wikimedia Commons

Researchers have discovered a mechanism by which Helicobacter pylori, the only known cancer-causing bacterium, disables a tumor suppressor protein in host cells.

Related Articles


The new study, in the journal Oncogene, reports the discovery of a previously unknown mechanism linking H. pylori infection and stomach cancer, the second leading cause of cancer deaths worldwide.

About two-thirds of the world's population is infected with H. pylori, a bacterium that can survive in the harsh environment of the stomach. Most infected people never develop disease. For a significant minority, however, infection with H. pylori leads to inflammation, ulcers and in some cases, stomach (gastric) cancer.

H. pylori's ability to cause disease is closely associated with a virulence protein called CagA. Previous studies have found that CagA-positive strains are much more likely to cause inflammation and spur the abnormal cell division and growth of cells that lead to cancer.

H. pylori injects CagA into the epithelial cells that line the stomach. Within the cells, CagA is able to hijack various signaling pathways and disrupt proper cellular functions.

Other studies have identified RUNX3 (pronounced RUNKS-three) as an important gastric cancer tumor suppressor.

Loss of expression of RUNX3 is causally associated with the development of gastric cancer, said University of Illinois medical biochemistry professor Lin-Feng Chen, who led the study. RUNX3 guards against tumor formation by spurring the production of factors that target unhealthy cells for destruction.

"Although emerging evidence suggests that RUNX3 is a tumor suppressor whose inactivation is involved in the initiation and progression of gastric cancer," the authors wrote, "the trigger for RUNX3 inactivation within gastric cells is largely unknown."

"The protein, RUNX3, is a transcription factor, so it activates different kinds of genes controlling cell growth and death," Chen said. "The first thing we wanted to see was whether H. pylori has any effect on the transcription activity of RUNX3."

Two graduate students in Chen's lab, Ying-Hung Nicole Tsang and Acacia Lamb, began the study by examining RUNX3 transcription activity in H. pylori-infected gastric epithelial cells. They found that infection with CagA-positive H. pylori inhibited the transcription activity of RUNX3 and reduced levels of the RUNX3 protein in cells. CagA-negative H. pylori had no effect on RUNX3 levels or activity.

"In fact, CagA alone is sufficient to down-regulate the RUNX3 transcription activity and reduce the expression of RUNX3, further supporting the importance of this bacterial protein in the genesis of gastric disease," Chen said.

Further tests revealed that CagA and RUNX3 physically interact with each other in human epithelial cells. The researchers found that a newly identified domain within CagA, the WW domain, recognizes a sequence in the RUNX3 protein known as the "PY motif." They further showed that this interaction leads to the "tagging" of RUNX3 for degradation via a process called ubiquitination.

Previous studies found that there are several unique sequences within the carboxyl-terminal region of CagA that are vital to the protein's ability to interact with host proteins and disrupt normal cellular processes.

"This is the first time anybody has identified a unique domain within the amino-terminal region of the CagA protein, and it will help us to better understand how this oncogenic protein functions," Chen said. "This study has uncovered a new step in the initiation of H. pylori-induced gastric cancer."

The accumulation of many deleterious changes in cells leads to the development of cancer. RUNX3 helps cells react when cellular processes go awry, so H. pylori-induced degradation of RUNX3 "could produce conditions in which aberrant cellular changes are less inhibited," Chen said.

Chen's group is working to identify the molecular mechanism by which CagA targets RUNX3 for degradation. He and his colleagues hope to design small molecules that can specifically inhibit the interaction between RUNX3 and CagA and block the degradation of RUNX3. Such drugs may be used to prevent the gastric diseases induced by H. pylori.

Researchers from the Vanderbilt University School of Medicine; Nagasaki University, in Japan; and the Institute of Molecular and Cell Biology, in Singapore, contributed to the research.

Partial funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tsang et al. Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene, 2010; DOI: 10.1038/onc.2010.304

Cite This Page:

University of Illinois at Urbana-Champaign. "Cancer-causing bacterium targets tumor-suppressor protein." ScienceDaily. ScienceDaily, 2 August 2010. <www.sciencedaily.com/releases/2010/08/100802073947.htm>.
University of Illinois at Urbana-Champaign. (2010, August 2). Cancer-causing bacterium targets tumor-suppressor protein. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2010/08/100802073947.htm
University of Illinois at Urbana-Champaign. "Cancer-causing bacterium targets tumor-suppressor protein." ScienceDaily. www.sciencedaily.com/releases/2010/08/100802073947.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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