Plaque-Causing Bacteria Shown to Promote Colorectal Cancer

Researchers at Columbia University report that Fusobacterium nucleatum—a common oral bacteria often implicated in tooth decay—is a colorectal cancer “facilitator”. Their research was published today in EMBO Reports. The findings could make it easier to identify and treat more aggressive colon cancers, they say. It also helps explain why some cases advance far more quickly than others.

Researchers have long known that colorectal cancer is caused by genetic mutations that typically accumulate over the course of a decade. "Mutations are just part of the story," says study leader Yiping W. Han, Ph.D. "Other factors, including microbes, can also play a role."

Han and his team have also demonstrated that about one-third of colorectal cancers are associated with F. nucleatum. Those cases are often the most aggressive, but nobody knew why. In a prior study, Han's research team discovered that the bacterium makes 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," says Han.

In the current study, the researchers found in cell cultures that noncancerous colon cells lack Annexin A1, which stimulates cancer growth. They then confirmed both in vitro and later in mice 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," says. Han. "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 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.

The researchers are currently looking for ways to develop Annexin A1 as a biomarker for more aggressive cancers and as a potential target for developing new treatments for colon and other types of cancer.