CELL
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2024
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IF 45.5
Kaili Fu,Alvin Ho Kwan Cheung,Chi Chun Wong,Weixin Liu,Yunfei Zhou,Feixue Wang,Pingmei Huang,Kai Yuan,Olabisi Oluwabukola Coker,Yasi Pan,Danyu Chen,Nga Man Lam,Mengxue Gao,Xiang Zhang,He Huang,Ka Fai To,Joseph Jao Yiu Sung,Jun Yu
Summary Streptococcus anginosus ( S. anginosus ) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus . Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
研究领域:
微生物学
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肿瘤学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2026
·
IF 5.5
Feng Li,Xiling Chen,Hao Huang,Xiaowei Sun,Maoyuan Wang,Haoyuan Xie,Jian Xie,Yunrui Dong,Weize Li,Meiyan Wu,Hongying Fan,Yang Bai
BackgroundGastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Although Helicobacter pylori (Hp) is considered a major etiological factor, only 3% of Hp-infected individuals develop GC, implying additional microbial drivers. Streptococcus anginosus (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.MethodsSA-EVs were isolated and characterized, followed by in vitro and in vivo functional assays, transcriptomic analysis and rescue experiments to explore their pro-tumor effects and key components.ResultsSA-EVs were efficiently internalized by GC cells, which markedly promoted GC cell proliferation, migration and invasion in vitro, and accelerated tumor growth in vivo. 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.ConclusionsStreptococcus 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.
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DOI
高影响因子
mBio
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2026
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IF 5.4
Luan Luan,Xiuling Song,Yunfei Zeng,Yunyun Xie,Yongxuan Hong,Jiawei Tang,Cong Ma,Bing Gu,Liang Wang
Gastric cancer remains a major global health burden, ranking fifth worldwide in both incidence and mortality. While Helicobacter pylori is a well-established Group I carcinogen, increasing evidence suggests that non-H. pylori bacteria, including Streptococcus anginosus, may also contribute to gastric carcinogenesis. However, their comparative pathogenic roles and interactions remain poorly defined. In this study, public databases showed stage-dependent abundance changes of H. pylori and S. anginosus but no significant correlation during gastric cancer progression. We further quantified both bacteria in gastric fluid samples collected from 500 individuals using a non-invasive gastric string test and in fecal samples from an independent cohort of 500 individuals by qPCR. In the two cohorts, no significant correlations were observed between the two bacterial pathogens, suggesting distinct colonization and pathogenic patterns. To evaluate functional differences, AGS cell co-culture models were established to explore their pro-tumorigenic effects. H. pylori predominantly exerted tumor-promoting effects through bacterial cell-associated mechanisms, whereas S. anginosus exerted stronger pro-tumorigenic effects via its metabolites. In particular, transcriptomic analysis revealed that proliferation-associated genes, including DEK and RTF1, were significantly upregulated by 21.9-fold and 19.2-fold, respectively, in cells treated with Streptococcus anginosus metabolite (SAM). Metabolomic profiling of SAM identified increased levels of spermidine and polyamine-related metabolites. Among these, N-acetylcadaverine, N-acetyltyrosine, N-acetyltryptophan, and urocanic acid were experimentally validated to significantly promote AGS cell proliferation. Collectively, these findings demonstrate that H. pylori and S. anginosus drive gastric tumorigenesis through contact-dependent and metabolite-mediated mechanisms, respectively, highlighting bacterial metabolites as emerging contributors to gastric cancer progression.
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产品关联
DOI
PubMed
高影响因子
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