By establishing the Fusobacterium nucleatum (F. nucleatum) infected-bone mesenchymal stem cells (BMSCs) transplantation model in APC^Min/+ mice, we investigated the role of BMSCs in the development of intestinal tumors induced by F. nucleatum. Apc^Min/++F. nucleatum + BMSCs mice showed increased susceptibility to intestinal tumors and accelerated tumor growth. BMSCs could also enhance tumor-initiating capability, invasive traits after F. nucleatum infection in vitro, and tumorigenicity in a nude murine model. Mechanistically, BMSCs were recruited to the submucosa, migrated to the mucosal layer, and might activate the canonical Wnt/β-catenin/TGIF axis signaling. Further mechanistic results illustrated increased production of the Wnt3a protein was found in Apc^Min/++F. nucleatum + BMSCs mice, and BMSCs were likely the major source of Wnt3a. Intriguingly, a deletion of Wnt3a via BMSC interference or antagonist analogs led to a significantly attenuated capacity of Apc^Min/++F. nucleatum mice to generate intestinal tumors. The findings suggest that BMSCs have the potential to migrate and accelerate F. nucleatum-induced colorectal tumorigenesis by modulating Wnt3a secretion; knockdown of BMSC-derived Wnt3a or antagonist analogs could attenuate carcinogenesis. Thus, Wnt3a might be a potential pharmaceutical target for the prevention and treatment of F. nucleatum-related colorectal cancer.

通过建立APC ^{Min / +}小鼠中的核杆菌（F. nucleatum）感染的骨间充质干细胞（BMSCs）移植模型，我们研究了BMSCs在由F. nucleatum诱导的肠道肿瘤发生中的作用。Apc ^{Min / +} + F. nucleatum  + BMSCs小鼠对肠道肿瘤的敏感性增加，并加速了肿瘤的生长。骨髓间充质干细胞还可以增强细胞的启动能力，核仁成虫侵袭性状体外感染和裸鼠模型的致瘤性。从机制上讲，BMSC被募集到粘膜下层，迁移到粘膜层，并可能激活经典的Wnt /β-catenin/ TGIF轴信号传导。进一步的机械结果表明，在Apc ^{Min / +} + F. nucleatum  + BMSCs小鼠中发现Wnt3a蛋白的产量增加，而BMSCs可能是Wnt3a的主要来源。有趣的是，通过BMSC干扰物或拮抗剂类似物缺失Wnt3a导致Apc ^{Min / +} + F. nucleatum小鼠产生肠道肿瘤的能力大大降低。研究结果表明，骨髓间充质干细胞具有迁移和加速核仁成纤维细胞的潜力-通过调节Wnt3a的分泌诱导大肠肿瘤发生；BMSC衍生的Wnt3a或拮抗剂类似物的基因敲低可减弱致癌作用。因此，Wnt3a可能是预防和治疗与核镰刀相关的大肠癌的潜在药物靶标。