The adhesin RadD enhances Fusobacterium nucleatum tumor colonization and colorectal carcinogenesis
Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here, we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to CRC cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-?B-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signaling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC. Overall design: To explore the downstream signaling pathway mediated by the RadD, we performed gene expression profiling of human colorectal camcer cell line HCT116 cells co-incubated with Fn WT and Fn ?radD. Sample C_1, C_2 and C_3 were from PBS-treated cell; Sample WT100_1, WT100_2 and WT100_3 were from Fn WT-treated cell with MOI100; Sample Delta100_1, Delta100_2 and Delta100_3 were from Fn ?radD-treated cell with MOI100.