Streptococcus anginosus extracellular vesicles deliver protein to promote gastric cancer progression.

BACKGROUND

Gastric 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.

METHODS

SA-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.

RESULTS

SA-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.

CONCLUSIONS

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.