A common oral bacteria often implicated in tooth decay accelerates the growth of colon cancer, a new US study has found.
The study by a team at the Columbia University College of Dental Medicine—and published in EMBO reports—could make it easier to identify and treat more aggressive colon cancers. It also helps explain why some cases advance far more quickly than others.
It’s long been known that colon cancer is caused by genetic mutations that typically accumulate over the course of a decade.
“Mutations are just part of the story,” study leader Professor Yiping W. Han said. “Other factors, including microbes, can also play a role.”
It’s also been demonstrated that about a third of colorectal cancers are associated with a common oral bacterium called F. nucleatum. Those cases are often the most aggressive, but nobody knew why.
In an earlier study, Professor Han’s research team discovered that the bacterium makes a molecule called FadA adhesin, triggering a signaling pathway in colon cells that has been implicated in several cancers. They also found that FadA adhesin only stimulates the growth of cancerous cells, not healthy cells.
“We needed to find out why F. nucleatum only seemed to interact with the cancerous cells,” Professor Han said.
In this latest study, the researchers found in cell cultures that noncancerous colon cells lack a protein, called Annexin A1, which stimulates cancer growth. They then confirmed that disabling Annexin A1 prevented F. nucleatum from binding to the cancer cells, slowing their growth.
The researchers also discovered that F. nucleatum increases production of Annexin A1, attracting more of the bacteria.
“We identified a positive feedback loop that worsens the cancer’s progression,” Professor Hand said. “We propose a two-hit model, where genetic mutations are the first hit. F. nucleatum serves as the second hit, accelerating the cancer signaling pathway and speeding tumor growth.”
The researchers then looked at an RNA-sequencing dataset, available through the National Center for Biotechnology Information of 466 patients with primary colon cancer. Patients with increased Annexin A1 expression had a worse prognosis, regardless of the cancer grade and stage, age, or sex.