Differential effect of Periodontal pathogen Fusobacterium nucleatum and Porphyromonas gingivalis on modulation of specific partial-EMT genes in colorectal cancer cells

ObjectiveWhile the epithelial-mesenchymal transition (EMT) is known to promote cancer stemness and metastasis, a hybrid partial EMT (p-EMT) state has recently been identified. This study examined the influence of Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) on p-EMT gene expression and their prognostic relevance in colorectal cancer (CRC).Materials and methodsHCT 116 cells were infected with Fn or Pg at an MOI of 100. Expression of p-EMT markers (SPP1, EMP3, INHBA, THBS2, ITGA5, P4HA2) and EMT-markers (ZEB1, SNAI1) was analyzed via RT-PCR after 6 hours (h) and 24 h. Cell migration was assessed using a scratch assay. TCGA data were used to validate gene expression in CRC patients, and Kaplan-Meier analysis was used to evaluate prognostic significance.ResultsPg infection induced a significant upregulation of EMP3 at the 24 h, while suppressing the expression of P4HA2, MXD1, and THBS2. The ZEB2 displayed a biphasic response, decreasing at 6 h before rising at 24 h, and SNAI1 was consistently suppressed. In contrast, Fn. infection resulted in the upregulation of ITGA5 and MMP3, accompanied by the downregulation of P4HA2, MXD1, MMP9, and SNAI1. Both enhanced cellular migration and wound closure capabilities. THBS2, CDH13, and P4HA2 were significantly elevated in tumor tissues compared to controls, while EMP3 and ZEB1 showed reduced expression. Elevated mRNA levels of EMP3, THBS2, and ITGA5 were significantly correlated with poorer overall survival.ConclusionFn and Pg can promote invasive phenotypes in CRC through distinct mechanisms, each modulating a unique subset of p-EMT and without instigating a complete, coordinated EMT gene signature.