A new way bacteria can cause cancer?
The idea that bacteria can induce cancer is not new – Helicobacter pylori, for example, is a well-known risk factor for stomach cancer. H. pylori It is thought to cause cancer by inducing persistent inflammation which, in turn, damages our DNA. Johnston, Bullman and Ting are suspected of a different mechanism, in which bacteria can alter or damage DNA and the genes that are turned on and off in normally altered cells.
Variables that alter the lettering of our DNA code can have a profound effect on whether a gene is turned on, turned off, loses an important tumor-destroying function, or acquires a new function. for tumor stimulation. Our cells can also use epigenetic alterations, which do not alter DNA sequence, to control which genes are turned on and off. Small epigenetic molecules called methyl groups are a type of DNA modification that, in humans, usually help turn on genes when they bind to the DNA strand.
“DNA methylation is one of the major global epigenetic changes we see throughout cancer,” Ting said. “There have been countless examples of how extreme methylation can suppress tumor suppressor genes, which in turn stimulate cancer development and cancer growth. ”
But it is usually unclear how these methylation changes begin.
“Yes a a lot of profitability, but there aren’t many concrete studies that identify how these changes are happening, ”said Ting. “This is one of the biggest issues in the field of medicine, and our unique project hopes to address it.”
Ting, Johnston and Bullman suggest that these cancer-causing methylation changes may arise from bacterial infestation. They suspect that certain bacteria can damage the DNA of our cells, including by altering their epigenetics and shutting down genes that normally inhibit tumor formation.
The Johnston lab focuses on the bacterial immune systems that the team can override with the DNA of our cells. They are enzymes that influence the presence or absence of methyl groups on DNA with a specific target sequence.
While these systems have evolved to protect bacteria against DNA from invading viruses, they can alter DNA – by cutting or shedding epigenetic molecules – from a non-bacterial species. be with the right sequence, including people. (Many decades before CRISPR, scientists co-opted the DNA-cutting capabilities of these systems to understand how genes work by cutting and passing different DNA sequences.)
It is one of the bacterial species known to produce these types of systems Fusobacterium nucleatum, which is often enriched in microbiome, or microbiota, colorectal tumors.
“Recent studies suggest that most hard tumors harbor microbiota inside a tumor, and each type of hard tumor has a specific microbiota inside a tumor,” Bullman said.
Bullman has shown that F. nucleatum they can enter human cells, and, once inside, move toward the nucleus, the organ-covered space where cells store their DNA. She also found that there were tumors with Fusobacteria in their microorganisms there are patterns of gene activity that are similar to altered methylation.
Was it caused by bacteria?
“Bacteria alter their DNA in completely different ways than human cells do, so it’s possible that there is a hidden set of information within human cancer DNA,” Johnston said.
The team suspects that bacteria could alter human DNA, by cutting it or adding to their own set of methyl groups. Could these mutations alter which genes are inverted?
“If this happens, and you weren’t looking for the specific reporting signs of bacterial changes, you could easily miss them,” he said.
Establishment support for high risk, high reward work
The team knows he’s going out right away. Government grant agencies such as National Institutes of Health prefer projects to be closer to the ground, scientifically speaking, but support from the WM Keck Foundation will get the project launched.
“When we got the funding, I went into the lab and said, ‘We finally have the money to turn science fiction into science fiction! ‘”Ting remembered.
The team aims to prove their hypothesis that bacteria can alter the epigenetics of our cells F. nucleatum in the context of colorectal cancer. The first step is to develop the tools and techniques they need to explore this new field.
If their hypothesis stops, the findings could shift to a paradigm in the three areas of scientists’ study, they said.
“It is rare for three scientists from very different fields to work together so meaningfully and deeply. When that happens, it’s very interesting, ”said Johnston.
About the WM Keck Foundation
The WM Keck Foundation was founded in 1954 in Los Angeles by William Myron Keck, founder of the Superior Oil Company. One of the largest philanthropic organizations in the country, the WM Keck Foundation supports science, engineering and medical research. The Foundation also supports undergraduate education and runs a program within Southern California to support arts and culture, education, health, and community service projects.