Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation

Abstract

ABSTRACTEnterococcus faecalisis a member of the intestinal and oral microbiota that may affect the etiology of colorectal and oral cancers. The mechanisms by whichE. faecalismay contribute to the initiation and progression of these cancers remain uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to play a crucial role in oral carcinogenesis. A link betweenE. faecalisand EGFR signaling in oral cancer has not been elucidated. The present study aimed to evaluate the association betweenE. faecalisand oral cancer and to determine the underlying mechanisms that linkE. faecalisto EGFR signaling. We report the high frequency ofE. faecalisinfection in oral tumors and the clinical association with EGFR activation. Using human oral cancer cells, we support the clinical findings and demonstrate thatE. faecaliscan induce EGFR activation and cell proliferation.E. faecalisactivates EGFR through production of H2O2, a signaling molecule that activates several signaling pathways. Inhibitors of H2O2(catalase) and EGFR (gefitinib) significantly blockedE. faecalis-induced EGFR activation and cell proliferation. Therefore,E. faecalisinfection of oral tumor tissues suggests a possible association betweenE. faecalisinfection and oral carcinogenesis. Interaction ofE. faecaliswith host cells and production of H2O2increase EGFR activation, thereby contributing to cell proliferation.