The unusual bacterial link between colorectal cancer and tooth decay
A common oral bacteria has been found to release a molecule that accelerates the growth of colorectal cancers. The impressive new research could lead to new cancer treatments as well as offer a valuable biomarker to help doctors identify potentially aggressive cancers.
Fusobacterium nucleatum, or F. nucleatum, is a common bacteria that plays a role in the accumulation of periodontal plaque. Previous research has found F. nucleatum enhances colorectal cancer growth in about one third of cases by triggering a signaling pathway in colon cells through a molecule called FadA adhesin. However, until now it was not known exactly why this specific process seemed to only stimulate the growth of cancer cells.
"We needed to find out why F. nucleatum only seemed to interact with the cancerous cells," explains Yiping Han, lead on the new study from the Columbia University College of Dental Medicine.
The new study reveals the key appears to be a specific protein called Annexin A1. In cell cultures the researchers found only cancerous colon cells expressed Annexin A1. This is important, as it was also discovered that FadA adhesin, the molecule expressed by F. nucleatum, stimulates cancer cell growth via an interaction with Annexin A1. This unique feedback loop between the bacteria and the cancer cell helps explain why F. nucleatum only enhances cancer cell growth and doesn't affect healthy cells.
"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."
To verify the results, the scientists examined RNA data from 466 patients with colorectal cancer. The data confirmed that those patients with the worst prognosis displayed higher rates of Annexin A1 expression. This affirmed the association between the protein and aggressive cancer growth.
It is important to note that this research is not suggesting colorectal cancer is caused by bad oral health. This is certainly not a case of simply brushing your teeth to prevent cancer, but instead it reveals a key mechanism that helps explain why some cancers tend to progress more rapidly in specific patients. In terms of a valuable biomarker, this research should help clinicians better identify patients that suffer from faster growing, and more aggressive cancers.
The research may also open the door to new treatments to slow cancer growth by targeting this particular pathway. Early experiments have revealed that disabling Annexin A1 in mouse models does result in a slowing of colorectal cancer growth.
The new research was published in the journal EMBO Reports.