How bacterial infections can lead to the development of cancer

Breaking new ground 5. jul 2022 2 min Assistant Professor Stavroula Hatzios Written by Kristian Sjøgren

New research suggests a mechanism that links infections with Helicobacter pylori to the development of cancer. The research shows that a bacterial infection inactivates a specific protein, and this is associated with tumour growth. The discovery improves the fundamental understanding of how bacterial infections can lead to cancer and how to prevent this.

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Viral and bacterial infections can lead to cancer.

The best example is infections with human papillomavirus (HPV), which are associated with an increased risk of developing cervical cancer.

H. pylori is another example, since these bacteria are associated with an increased risk of developing gastric cancer, a very common type of cancer globally that is often fatal.

Now a new study sheds light on some apparent mechanisms by which H. pylori leads to the development of cancer.

The research shows that H. pylori infection modifies some proteins that affect tumour growth, altering at least one protein in a way that causes rapid growth.

“This study linked H. pylori infection to the modification of proteins that regulate tumour growth. This opens up the possibility of detecting modified proteins as biomarkers for the early development of cancer, and the proteins themselves may become targets for future cancer treatment,” explains a researcher behind the study, Stavroula Hatzios, Assistant Professor, Yale University, New Haven, Connecticut, USA.

The research has been published in Nature Chemical Biology.

Bacteria and proteins may interact in the development of cancer

Researchers have long known that bacterial or viral infections can affect people’s DNA and thus lead to various types of cancer.

H. pylori infections can affect proteins in a way that promote the development of cancer.

Stavroula Hatzios says that H. pylori could perhaps modify a protein and thereby alter its effect on signalling pathways that affect the development of cancer.

“We know that bacterial infections can cause the immune system and other cells in the body to produce more free radicals. We had the idea that these free radicals might negatively affect various proteins and thereby contribute to the risk of developing cancer,” she explains.

Changes in proteins may lead to cancer

In the study the researchers used various advanced techniques to identify all the proteins in individual cells. The same techniques can also identify which proteins have been altered from their normal form.

The researchers identified many proteins modified by oxygen free radicals that increase in concentration in connection with H. pylori infection. Many of these proteins also have known roles in developing cancer.

The researchers selected one protein and determined how H. pylori infection affects it.

The protein is called legumain and is produced in large quantities by various types of cancer cells, but it had not previously been linked to H. pylori infection.

The researchers found that infections lead to oxidative stress in the cells that increase the presence of oxygen free radicals and thereby modify a specific site on legumain and inactivate it inside the cell. This also increases the possibility of legumain being secreted from the cell into the environment.

“The modification leads to changes in the activity of the protein and its location. We have shown in mouse experiments that making a similar genetic change in legumain leads to dramatic tumour growth. It is quite interesting that a simple change in a protein can have this effect and that the same change can occur in an infection with H. pylori,” says Stavroula Hatzios.

Diagnosing cancer sooner?

Stavroula Hatzios thinks that the discovery may strongly influence both the understanding of how bacterial infections promote the development of cancer and the potential role of modified proteins in this process.

She thinks that the first step should be to determine whether, for example, legumain can be used as a biomarker for the infection-related development of cancer.

This might enable screening for the cancer-promoting changes in legumain very early in the disease trajectory.

“People are usually infected with H. pylori in childhood, but decades elapse before cancer develops. We do not know who will develop cancer, but changes in proteins such as legumain may point us in the right direction,” explains Stavroula Hatzios.

More broadly, the discovery can also be used to expand the scope of research in terms of understanding how bacterial infections lead to cancer and the role of modified proteins in the risk of cancer.

“We have shown that there is a whole new world to explore. If we can identify proteins that contribute to the development of cancer after infection, it opens up the possibility of designing completely new tools to detect and treat this devastating disease,” concludes Stavroula Hatzios.

An infection-induced oxidation site regulates legumain processing and tumor growth” has been published in Nature Chemical Biology. The Novo Nordisk Foundation contributed to funding the research through a Challenge Programme grant to a consortium that includes co-author Manuel R. Amieva.

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