Potential mechanisms underlying Enterococcus faecalis-driven pancreatic cancer cell proliferation

The development of various cancers is intricately linked with the human microbiome. Recent studies have highlighted a substantial association between pancreatic cancer and gut microbiota. However, the specific roles and underlying regulatory mechanisms of individual gut microbial species in pancreatic cancer progression remain poorly understood. Enterococcus faecalis, a common member of the human commensal microbiota, has been found to be enriched in the tumor tissues of pancreatic cancer patients. However, its functional contribution has not been clearly defined. In this study, we established a co-culture system involving E. faecalis and pancreatic cancer cells. Our results show that E. faecalis promoted the proliferation, migration, and invasion of pancreatic cancer cells. Following pre-treatment with E. faecalis, the phosphorylation level of epidermal growth factor receptor (EGFR) was markedly elevated. Inhibition of EGFR effectively suppressed the pro-proliferative effects induced by E. faecalis. Further investigation revealed that E. faecalis stimulated the production of reactive oxygen species (ROS) in pancreatic cancer cells. This ROS production might be sensed by Toll-like receptors (TLRs), leading to the activation of the EGFR signaling pathway. When cells were incubated with TLR inhibitors or ROS scavengers, both EGFR expression and its downstream pro-proliferative effects were significantly attenuated. Collectively, this study provides mechanistic insights into how E. faecalis contributes to pancreatic cancer progression and offers new perspectives for the development of diagnostic and therapeutic strategies targeting this microbial signaling pathway.