Researchers at the Columbia University College of Dental Medicine have determined how
F. nucleatum
-- a common oral bacteria often implicated in tooth decay --
accelerates the growth of colon cancer. The study was published online
in the journal
EMBO Reports.
Why it matters
The findings 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, thanks to the same bacteria found in
dental plaque.
Background
Colon cancer is the second leading cause of cancer death in the U.S.
Researchers have long known that the disease 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,
PhD, professor of microbial sciences at Columbia University's College
of Dental Medicine and Vagelos College of Physicians & Surgeons.
"Other factors, including microbes, can also play a role."
Scientists have also 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 a
prior study, 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," says Han.
What the study found
In the current study, the researchers found in cell cultures that
noncancerous colon cells lack a protein, called 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."
Clinical implications
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.
Next steps
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.