{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:57Z","timestamp":1790747697752,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370139"],"award-info":[{"award-number":["32370139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Although\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      (Hp) is considered a major etiological factor, only 3% of Hp-infected individuals develop GC, implying additional microbial drivers.\n                      <jats:italic>Streptococcus anginosus<\/jats:italic>\n                      (SA) exhibits independent pro-carcinogenic properties, but its mechanism in regulating GC malignant phenotypes remains elusive. This study investigated the roles and molecular mechanisms of SA-derived extracellular vesicles (SA-EVs) in GC progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SA-EVs were isolated and characterized, followed by\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      functional assays, transcriptomic analysis and rescue experiments to explore their pro-tumor effects and key components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SA-EVs were efficiently internalized by GC cells, which markedly promoted GC cell proliferation, migration and invasion\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and accelerated tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Mechanistically, the protein cargos of SA-EVs specifically triggered the activation of the JAK-STAT signaling pathway, which further upregulated the expression of genes associated with cell proliferation and epithelial-mesenchymal transition (EMT). Moreover, pharmacological inhibition experiments verified that removal of SA-EV protein components or pharmacological blockade of JAK-STAT signaling effectively eliminate the pro-tumor effects of SA-EVs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Streptococcus serves as a core signature genus in Hp-independent GC. SA drives GC malignancy by delivering functional proteins via EVs to activate JAK-STAT signaling. This study reveals a novel bacteria-host interaction mechanism mediated by SA-EVs, providing a potential target for GC intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1917293","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:31Z","timestamp":1790744191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Streptococcus anginosus extracellular vesicles deliver protein to promote gastric cancer progression"],"prefix":"10.3389","volume":"16","author":[{"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiling","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyuan","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunrui","family":"Dong","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weize","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Baiyun District People\u2019s Hospital of Guangzhou, Guangzhou","place":["Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B10","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/sla.0000000000005587","article-title":"A novel microbiome signature in gastric cancer: A two independent cohort retrospective analysis","volume":"276","author":"Abate","year":"2022","journal-title":"Ann. 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