ST3GAL1 mediates sialylation to promote adhesion of Fusobacterium nucleatum to colorectal cancer cells.

Fusobacterium nucleatum is a commensal bacterium in the oral cavity and is closely related to several oral infectious diseases. In addition to oral colonization, F. nucleatum is enriched in colorectal cancer (CRC) and is closely associated with CRC progression, while the mechanism of F. nucleatum adhesion to cancer cells has not been fully explained. Sialylation is of high levels in CRC and host cell surface sialoglycans are considered as potential targets for microorganism adhesion. However, the effect of excessive sialylation in CRC on the adhesion of gut microorganisms remains unknown. Here we found that high sialylation level mediated by ST3GAL1 in CRC is closely associated with F. nucleatum adhesion. Knockdown or overexpression of ST3GAL1 significantly affected F. nucleatum adhesion level in vitro and in vivo. In addition, F. nucleatum enables its colonization and cancer-promoting effect via upregulation of H3K27 acetylation and ANGPTL4 expression. Together, our study revealed a link between host sialylation and F. nucleatum adhesion, providing a new insight into F. nucleatum intratumoral retention and persistence in CRC.