Potential mechanisms underlying Enterococcus faecalis-driven pancreatic cancer cell proliferation - Abstract

Sep 22, 2026

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Pancreatic cancer is linked to the human microbiome, yet the roles of individual gut microbial species and their regulatory mechanisms in disease progression remain unclear. Enterococcus faecalis is enriched in pancreatic tumor tissues. Using an E. faecalis–pancreatic cancer co-culture system, the study shows enhanced cancer-cell proliferation, migration, and invasion, mediated by EGFR phosphorylation. EGFR inhibition blocks these effects.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

Study design and main findings

Proposed signaling mechanism

Clinical relevance and significance

| Host-Microbial Interactions | Research Article Potential mechanisms underlying Enterococcus faecalis-driven pancreatic cancer cell proliferation Minghan Guan,1 Xiaoyu Guo,1 Mengzhen Kong,1 Yang Qin,1 Hua Xu,2 Xiaomin Su,2 Pan Wang,1 Xiaobing Wang1 AUTHOR AFFILIATIONS See affiliation list on p. 15. ABSTRACT 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. IMPORTANCE A diverse microbiome is closely associated with cancer, as bacterial presence has been detected in the majority of solid tumors. However, the composition, abundance, and functional profiles of the microbiota vary significantly across different tumor types, thereby exerting distinct effects on tumorigenesis and disease progression. Recent studies have shown that pancreatic cancer hosts a variety of bacterial populations, including gut-derived bacteria that may translocate to pancreatic tissue via mesenteric venous or lymphatic drainage pathways. For example, Enterococcus and Enterobacter species have been identified in the cyst fluid of patients with pancreatic cystic neoplasms. Moreover, antibodies against Enterococcus faecalis capsular polysaccharide have been detected in the sera of patients with pancreatitis and pancreatic cancer, and E. faecalis has been observed in pancreatic ducts. Despite these observations, the precise mechanisms through which E. faecalis influences pancreatic cancer remain unclear. Our study demonstrates that E. faecalis promotes pancreatic cancer cell proliferation through the activation of the Toll-like receptor-reactive oxygen species-epidermal growth factor receptor signaling pathway. KEYWORDS pancreatic cancer, E. faecalis, cell proliferation, cell migration, EGFR Editor Yiping W. Han, Columbia University, New York, New York, USA Address correspondence to Xiaobing Wang, [wangxiaobing@snnu.edu.cn](wangxiaobing@snnu.edu.cn), or Xiaomin Su, [sufeichi112@163.com](sufeichi112@163.com). authors declare conflict of interest P ancreatic cancer is an exceptionally lethal malignancy, with rising incidence and mortality rates worldwide. Pancreatic ductal adenocarcinoma (PDAC), the most common subtype, accounts for about 90% of cases (1) . Current understanding of PDACpathogenesis remains limited, and the absence of reliable biomarkers for early detection, as well as effective preventive and therapeutic strategies,

FAQs

How does Enterococcus faecalis affect pancreatic cancer cells?

E. faecalis increases pancreatic cancer cell proliferation, migration, and invasion in co-culture experiments.

What role does EGFR play in E. faecalis–induced effects?

E. faecalis pre-treatment markedly elevates EGFR phosphorylation, and EGFR inhibition suppresses the pro-proliferative effects.

What mechanism links E. faecalis to EGFR activation?

E. faecalis stimulates reactive oxygen species (ROS) production, which is proposed to be sensed by Toll-like receptors (TLRs), activating EGFR signaling. ROS scavengers or TLR inhibitors reduce EGFR expression and downstream pro-proliferative effects.

Sep 22, 2026

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