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Potential mechanisms underlying Enterococcus faecalis-driven pancreatic cancer cell proliferation
Minghan Guan1, Xiaoyu Guo1, Mengzhen Kong1
1National Engineering Laboratory for Resource Development of Endangered Chinese Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, Shaanxi Normal University, Xi'an, China.
Enterococcus faecalis, a gut bacterium, promotes pancreatic cancer growth by activating the Toll-like receptor-reactive oxygen species-epidermal growth factor receptor pathway. This finding offers new therapeutic targets for pancreatic cancer treatment.
Area of Science:
- Microbiology and Oncology
- Gut Microbiome and Cancer Biology
Background:
- The human microbiome is linked to cancer development, with specific associations found between pancreatic cancer and gut microbiota.
- While Enterococcus faecalis is enriched in pancreatic tumors, its precise role in cancer progression is unclear.
Purpose of the Study:
- To investigate the functional contribution of Enterococcus faecalis in pancreatic cancer progression.
- To elucidate the underlying molecular mechanisms by which E. faecalis influences pancreatic cancer cells.
Main Methods:
- Co-culture system of E. faecalis and pancreatic cancer cells.
- Analysis of epidermal growth factor receptor (EGFR) phosphorylation.
- Assessment of reactive oxygen species (ROS) production and Toll-like receptor (TLR) signaling.
- Use of EGFR inhibitors, TLR inhibitors, and ROS scavengers.
Main Results:
- E. faecalis significantly promoted pancreatic cancer cell proliferation, migration, and invasion.
- E. faecalis induced EGFR phosphorylation, which was reversed by EGFR inhibition.
- E. faecalis stimulated ROS production, leading to TLR activation and subsequent EGFR pathway activation.
Conclusions:
- E. faecalis promotes pancreatic cancer progression through the TLR-ROS-EGFR signaling axis.
- These findings provide mechanistic insights into the role of gut microbiota in pancreatic cancer.
- The study suggests potential diagnostic and therapeutic strategies targeting this microbial signaling pathway.
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