Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes

Abstract

Background Fusobacterium nucleatum was previously found to become a dominant species in the gastric cancer-associated microbiota of patients from Taiwan. However, the prevalence of Fusobacterium nucleatum infection in gastric cancer has not been examined in a larger patient cohort. In addition, whether Fusobacterium nucleatum elicits a cellular response in gastric cancer remains unknown.Methods A study cohort of resected gastric cancer tissue specimens was examined using nested PCR to detect Fusobacterium nucleatum. In vitro coculture of Fusobacterium nucleatum was carried out to identify the alteration in the expression profile of patient-derived gastric cancer cell line.Results approximately one-third of gastric cancer tissues are positive for Fusobacterium nucleatum. Statistical analysis showed that the risk for Fusobacterium nucleatum infection is increased in late-stage cancer tissue specimens and incurs poorer survival in Helicobacter pylori-positive patients. In vitro coculture experiment shows a drastic interferon response activated only by a high multiplicity of infection, and the response peaks within 24 hours and subsides after 72 hours of incubation. Another set of response genes is the continuous increase of actins and their regulators with prolonged time of incubation, activated by both low and high multiplicity of infection.Conclusions Our data indicates that Fusobacterium nucleatum incites an inflammatory response from the cancer cells and promotes cell mobility, likely