Tumor Targeting by Fusobacterium nucleatum: A Pilot Study and Future Perspectives

Abstract

Colorectal adenocarcinoma (CRC) is a common tumor with high mortality rates. Interestingly, CRC was found to be colonized by the oral anaerobic bacteria Fusobacterium nucleatum, which accelerates tumor progression and enables immune evasion. The CRC-specific colonization by fusobacteria is mediated through the recognition of tumor displayed Gal-GalNAc moieties by the fusobacterial Fap2 Gal-GalNAc lectin. Here, we show high Gal-GalNAc levels in additional adenocarcinomas including those found in the stomach, prostate, ovary, colon, uterus, pancreas, breast, lung, and esophagus. This observation coincides with recent reports that found fusobacterial DNA in some of these tumors. Given the tumorigenic role of fusobacteria and its immune evasion properties, we suggest that fusobacterial elimination might improve treatment outcome of the above tumors. Furthermore, as fusobacteria appears to specifically home-in to Gal-GalNAc—displaying tumors, it might be engineered as a platform for treating CRC and the above common, lethal, adenocarcinomas.

Differences in mortality in Fusobacterium necrophorum and Fusobacterium nucleatum infections detected by culture and 16S rRNA gene sequencing

“…A few studies have investigated the underlying pathomechanisms for the apparent prevalence of Fusobacteria in cancers. The spread of oral Fusobacteria to the colorectal cancer is thought to be enabled by a transient bacteremia, such as those seen in Fusobacterium infections [16]. The All the above studies, including our study, suggest that Fusobacteria play an important part in the human microbiome of the gut, and the pathomechanisms regarding colorectal cancer evolution and growth.…”

“…These data suggest a link, also in lung cancer, between the bacterial constitution and the cancer. To support this, a recent study compiled data, that suggest that through the Gal-GalNAc, Fusobacteria may be linked to many different cancers, including breast, lung and esophagus cancers [16]. Further studies in lung cancer are required to confirm this hypothesis.…”

Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal cancer

“…3 ). Interestingly, these taxa are commonly found in patients with CRC 57 , with the Fusobacterium genus frequently being associated with tumor progression 58 . Moreover, CpT samples possessed microbial genera commonly involved in development of intestinal disease or pathologies, such as Streptococcus (taxonomic trend prevalence of 80.00% in CpT) and Gemella (taxonomic trend prevalence of 80% in CpT) 59 , 60 .…”

“…Our metagenomic analysis revealed that CpT samples had a higher abundance of the Fusobacteria phylum compared to healthy samples. Interestingly, the Fusobacterium genus is often involved in tumor progression 58 , 70 .…”

Antiproliferative Effects of Short-chain Fatty Acids on Human Colorectal Cancer Cells via Gene Expression Inhibition

“…The results of this study suggest that colorectal carcinogenesis may be significantly suppressed by sustained intake of food such as probiotics or prebiotics. In contrast, Fusobacterium nucleatum has attracted attention as the cause of colorectal cancer (21)(22)(23). For example, FadA Adhesin, a fungal component of the nucleatum, degrades E-cadherin on the cell membrane and binds to β-catenin via p120 to activate oncogenic signalling via pathways such as Wnt/β-catenin (24).…”