Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
BMC Oral Health. 2024 May 2;24(1):518. doi: 10.1186/s12903-024-04252-3.
Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown.
In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments.
Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention.
Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.
具核梭杆菌（F. nucleatum）是一种微生物风险因素，其存在增加了口腔鳞状细胞癌（OSCC）进展的风险。然而，它是否能促进 OSCC 细胞的增殖尚不清楚。
在这项研究中，我们使用体外和体内实验研究了 F. nucleatum 对 OSCC 细胞增殖的影响。
我们的结果表明，F. nucleatum 促进了 OSCC 细胞的增殖，在 72 小时（CCK-8 测定）后使细胞数量增加了一倍。细胞周期分析显示 G2/M 期阻滞。F. nucleatum 与 CDH1 的相互作用触发了磷酸化，上调了下游蛋白β-catenin，并激活了 cyclinD1 和 Myc。值得注意的是，F. nucleatum 不会影响非癌细胞，与 CAL27 细胞中 CDH1 的表达水平无关。在 293T 细胞中过表达磷酸化的 CDH1 不会上调β-catenin 和与周期相关的基因。体内 BALB/c 裸鼠实验表明，F. nucleatum 干预后肿瘤体积和 Ki-67 增殖指数增加。
我们的研究表明，F. nucleatum 通过 CDH1/β-catenin 通路促进 OSCC 细胞增殖，加深了我们对其在 OSCC 进展中的作用的理解，并强调了其作为治疗靶点的潜力。
