Bacterial extracellular vesicles from Streptococcus mutans drive OSCC progression through β-catenin signaling

Area of Science:

• Microbiology
• Oncology
• Cell Biology

Background:

• Oral squamous cell carcinoma (OSCC) is aggressive, with microbial dysbiosis implicated.
• The role of bacterial extracellular vesicles (EVs) in OSCC pathogenesis is unclear.

Purpose of the Study:

• To investigate if Streptococcus mutans-derived EVs (SmEVs) influence OSCC progression.
• To identify the mechanisms by which SmEVs affect OSCC.

Main Methods:

• Isolation and characterization of SmEVs.
• In vitro studies using CAL-27 OSCC cells and in vivo studies using a nude-mouse xenograft model.
• Transcriptomic analysis, functional loss-of-experiments (β-catenin silencing), DIA proteomics, and in silico docking.

Main Results:

• SmEVs were internalized by OSCC cells, enhancing proliferation, migration, and invasion.
• SmEV exposure activated the Wnt/β-catenin signaling pathway, increasing β-catenin, TCF7, and FOSL1/Fra-1.
• β-catenin was essential for SmEV-induced effects; its silencing abrogated proliferation, migration, and TCF7/Fra-1 activation.
• SmEVs accelerated tumor growth in vivo and reinforced β-catenin axis activation.

Conclusions:

• S. mutans-derived EVs promote OSCC progression via β-catenin-driven transcriptional programs.
• Specific SmEV proteins are potential mediators and therapeutic targets for OSCC.