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 colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K–AKT–NF–κB–MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling 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.

有核梭杆菌可以与宿主细胞结合并增强肠道肿瘤的发生。在这里，我们使用全基因组筛选来鉴定粘附素 RadD，它可以促进具核梭菌在体外粘附到结直肠癌 (CRC) 细胞上。 RadD 直接与 CD147（一种在 CRC 细胞表面过度表达的受体）结合，启动 PI3K-AKT-NF-κB-MMP9 级联反应，随后增强小鼠的肿瘤发生。临床样本分析表明，CRC 组织中radD基因水平升高与致癌信号激活和患者预后不良呈正相关。最后，阻断小鼠体内 RadD 和 CD147 之间的相互作用可有效削弱具核梭杆菌的附着并减弱具核梭杆菌诱导的致癌反应。总之，我们的研究提供了对F. nucleatum RadD 驱动的致癌机制的见解，并表明 RadD-CD147 相互作用可能是 CRC 的潜在治疗靶点。