Researchers uncover how oral bacteria can affect the aggressiveness of colon cancers

Colon cancer is the second leading cause of cancer-related deaths 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,” according to study leader Dr. Yiping W. Han, Professor of Microbial Sciences at the Columbia University College of Dental Medicine and Vagelos College of Physicians and Surgeons. “Other factors, including microbes, can also play a role.”

In the study, the researchers found in cell cultures that noncancerous colon cells lack a protein called annexin A1, which stimulates cancer growth. They also discovered that F. nucleatum increases production of annexin A1, attracting more of the bacteria. They next confirmed that disabling annexin A1 prevented F. nucleatum from binding to the cancer cells, slowing their growth. “We identified a positive feedback loop that worsens the cancer’s progression,” said 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.”

To further investigate their findings, the researchers then looked at an RNA-sequencing data set, available through the National Center for Biotechnology Information, of 466 patients with primary colon cancer. Patients with increased annexin A1 expression had a poorer prognosis, regardless of the cancer grade and stage, or their age or sex.

With the initial research results having recently been published, the scientists are now 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.

The study, titled “Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1,” was published in EMBO reports on March 4, 2019.

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