{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:49Z","timestamp":1785411529262,"version":"3.56.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373109"],"award-info":[{"award-number":["82373109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shaanxi Provincial Key Research and Development Project","award":["2024SF-YBXM-405"],"award-info":[{"award-number":["2024SF-YBXM-405"]}]},{"name":"Science and Technology Plan Project of Xi\u2019an","award":["21YXYJ0083"],"award-info":[{"award-number":["21YXYJ0083"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      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.\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      , 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\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      and pancreatic cancer cells. Our results show that\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      promoted the proliferation, migration, and invasion of pancreatic cancer cells. Following pre-treatment with\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      , the phosphorylation level of epidermal growth factor receptor (EGFR) was markedly elevated. Inhibition of EGFR effectively suppressed the pro-proliferative effects induced by\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      . Further investigation revealed that\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                      contributes to pancreatic cancer progression and offers new perspectives for the development of diagnostic and therapeutic strategies targeting this microbial signaling pathway.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        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,\n                        <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Enterobacter<\/jats:italic>\n                        species have been identified in the cyst fluid of patients with pancreatic cystic neoplasms. Moreover, antibodies against\n                        <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                        capsular polysaccharide have been detected in the sera of patients with pancreatitis and pancreatic cancer, and\n                        <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                        has been observed in pancreatic ducts. Despite these observations, the precise mechanisms through which\n                        <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                        influences pancreatic cancer remain unclear. Our study demonstrates that\n                        <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                        promotes pancreatic cancer cell proliferation through the activation of the Toll-like receptor-reactive oxygen species-epidermal growth factor receptor signaling pathway.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03963-25","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:00:20Z","timestamp":1781182820000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Potential mechanisms underlying\n                    <i>Enterococcus faecalis<\/i>\n                    -driven pancreatic cancer cell proliferation"],"prefix":"10.1128","volume":"17","author":[{"given":"Minghan","family":"Guan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0170z8493","id-type":"ROR","asserted-by":"publisher"}],"name":"National 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","place":["Xi'an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Guo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0170z8493","id-type":"ROR","asserted-by":"publisher"}],"name":"National 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","place":["Xi'an, 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