Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis

Area of Science:

• Microbiology
• Oncology
• Oral Pathology

Background:

• Parvimonas micra (P. micra) is an opportunistic oral pathogen linked to various cancers.
• Limited research exists on P. micra's specific role in oral squamous cell carcinoma (OSCC).

Purpose of the Study:

• To investigate the association between P. micra and OSCC.
• To elucidate the mechanisms by which P. micra promotes OSCC metastasis.
• To identify potential therapeutic targets.

Main Methods:

• Analysis of P. micra enrichment in OSCC tissues.
• Investigation of P. micra's effects on hypoxia, glycolysis, and autophagy.
• Identification of the P. micra surface protein TmpC and its interaction with OSCC receptor CKAP4.
• In vitro and in vivo experiments using masitinib and antibodies to target the TmpC-CKAP4 interaction.

Main Results:

• P. micra is enriched in OSCC tissues and correlates with tumor metastasis and stage.
• P. micra infection induces hypoxia/HIF-1α, glycolysis, and autophagy, promoting OSCC metastasis.
• The P. micra protein TmpC binds to the OSCC receptor CKAP4, facilitating bacterial invasion.
• This interaction activates HIF-1α and autophagy via CKAP4-RanBP2 and CKAP4-NBR1 pathways.
• Targeting CKAP4 with masitinib or antibodies inhibited P. micra attachment and metastasis.

Conclusions:

• P. micra promotes OSCC metastasis through the TmpC-CKAP4 interaction, inducing key signaling pathways.
• The TmpC-CKAP4 interaction represents a potential therapeutic target for managing OSCC metastasis.