Fusobacterium nucleatum and cancer

Abstract

Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in the progression of an increasing number of tumors types. Thus far, the mechanisms underlying tumor exacerbation by F. nucleatum include the enhancement of proliferation, establishment of a tumor-promoting immune environment, induction of chemoresistance, and the activation of immune checkpoints. This review focuses on the mechanisms that mediate tumor-specific colonization by fusobacteria. Elucidating the mechanisms mediating fusobacterial tumor tropism and promotion might provide new insights for the development of novel approaches for tumor detection and treatment.

Keywords: Fusobacterium nucleatum; oncobacteria; oncobiont; pathobiont.

FIGURE 1

F. nucleatum acts as a bridging organism in dental plaques. A. Scanning electron microscopic image of a multispecies human oral biofilm. B. Schematic representation showing the ability of F. nucleatum to function as a “bridging” organism connecting the early colonizers, such as Streptococcus species via the RadD adhesin, and the largely anaerobic secondary colonizers, including Porphyromonas gingivalis via Fap2, Treponema denticola, and Aggregatibacter actinomycetemcomitans

FIGURE 2

Gal‐GalNAc levels are increased in human adenocarcinomas. (A) Tumors are arranged according to increasing Gal‐GalNAc levels. Examined adenocarcinomas that displayed high levels of Gal‐GalNAc are marked with dark gray (right). (B) Gal‐GalNAc levels in the tumors (shaded dots) described in (A) were compared to those in matched normal tissue controls (hollow dots). Of the nine examined adenocarcinomas, seven showed significantly higher Gal‐GalNAc levels than the matched control tissues. The normal tissue controls for the esophagus, lung, and skin were used twice for the respective esophagus adenocarcinoma and esophagus squamous cell carcinoma (Esophagus SCC), the respective lung adenocarcinoma and lung SCC, and for the melanoma and SCC. Each symbol represents the fluorescent intensity of a sample from different patient. Data are presented as the mean ± SEM (*P < .05, **P < .01, ***P = .0001 analyzed by two‐tailed Mann‐Whitney test; ****P < .0001 analyzed by two‐tailed t‐test). This figure is from reference

FIGURE 3

Breast cancer colonization by F. nucleatum. Schematic representation depicting the mechanism of the translocation of oral F. nucleatum to breast tumor via blood circulation. The bacterial lectin Fap2 enables the specific binding of F. nucleatum to cancerous cells that over‐display Gal‐GalNAc

FIGURE 4

Various mechanisms utilized by F. nucleatum to accelerate tumor progression. The fusobacterial Fap2 domain binds tumor‐displayed Gal‐GalNAc to enable tumor colonization., Tumor acceleration is then mediated with the following mechanisms