Porphyromonas Gingivalis Promotes Oral Squamous Cell Carcinoma Metastasis Through Migrasomes

Porphyromonas gingivalis is a critical mediator that modulates oral squamous cell carcinoma (OSCC) progression in addition to genetic, epigenetic, and microenvironmental elements. Emerging trends imply that P. gingivalis can promote OSCC metastasis by affecting cell adhesion, polarization, epithelial-to-mesenchymal transition, etc. Migrasomes are newly discovered extracellular vesicles that play a key role in mediating cancer metastasis. Here, we investigated the effects of P. gingivalis on migrasome formation in OSCC cells and explored the functional significance and potential molecular mechanisms of P. gingivalis in mediating migrasome formation. Migrasomes were detected by scanning electron microscopy and immunofluorescence. Live P. gingivalis fluorescence imaging was achieved by transforming an RNA aptamer into the bacterial genome. The localization of live P. gingivalis in primary and metastatic OSCC foci was determined via freeze-slicing technology in an HSC-3 cell xenograft tongue tumor mouse model. Using transcriptome sequencing, western blotting, RNA interference, and immunohistochemistry, the molecular mechanisms underlying how P. gingivalis affects migrasome formation were investigated both in vitro and in vivo. P. gingivalis promoted the formation of migrasomes in HSC-3 cells and OSCC lung metastases. After P. gingivalis infection, the levels of phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (PIP5K1A) and phosphatidylinositol (4,5)-bisphosphate (PIP2). PIP2 recruited the small GTPase Rab35 to the migrasome site and promoted endocytosis of P. gingivalis into HSC-3 cells. P. gingivalis promotes OSCC lung metastasis by stimulating PIP5K1A-regulated migrasome formation. Targeting P. gingivalis will yield valuable insight into the clinical management of OSCC.