Tohoku J. Exp. Med., 2021 April, 253(4)

Fusobacterium nucleatum Promotes Cisplatin-Resistance and Migration of Oral Squamous Carcinoma Cells by Up-Regulating Wnt5a-Mediated NFATc3 Expression

Jingshu Da,1 Xiaoqian Wang,1,2 Lu Li1,2 and Yan Xu1,2

1Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, Jiangsu, China
2Department of Periodontology, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Bacterial infection contributes to tumor development and malignant progression. Fusobacterium nucleatum (F. nucleatum) is reported to promote oral squamous cell carcinoma. However, molecular bases of F. nucleatum regulating oral cancer cells have not been fully elucidated. We report here that F. nucleatum down-regulates p53 and E-cadherin via the Wnt/NFAT pathway to promote cisplatin-resistance and migration in oral squamous carcinoma cells. We pretreated Cal-27 and HSC-3 cells with F. nucleatum and the survival rates against cysplatin (Cis-diamminedichloroplatinum, CDDP) were significantly higher in treated cells. The expressions of migration and apoptosis-related proteins like E-cadherin and p53 were lower in western blot analysis. We observed that F. nucleatum was an activator of the Wnt/NFAT pathway. The expression levels of the Wnt pathway gene wnt5a and Nuclear factors of activated T cells 3 (NFATc3) were notably higher in treated cells. With the inhibition effect of NFAT-inhibitory peptide VIVIT, the expressions of E-cadherin and p53 in response to F. nucleatum infection were up-regulated reversely. We concluded that F. nucleatum might promote cisplatin-resistance and migration of oral squamous cell carcinoma cells through the Wnt/NFAT pathway.

Key words —— cisplatin-resistance; Fusobacterium nucleatum; migration; oral squamous cell carcinoma; Wnt5a/NFATc3

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Tohoku J. Exp. Med 2021, 253, 249-259.

Correspondence: Yan Xu, Ph.D., Department of Periodontology, Affiliated Stomatological Hospital of Nanjing Medical University, No.1 Shanghai Road, Nanjing, Jiangsu 210029, China.

e-mail: yanxu_group@163.com