FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

Cell & Bioscience

Ke Liu¹  Zhengjun Shang¹  Yang Chen²  Weilian Liang² 

[1] Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, 430079, Wuhan, China;The State Key Laboratory Breeding Base of Basic Science of Stomatology, Hubei Province and Key Laboratory of Oral Biomedicine (Wuhan University), Ministry of Education (Hubei-MOST KLOS & KLOBM), Wuhan, China;

关键词: FOXD1;    EMT;    STEMNESS;    SNAI2;    OSCC;   

DOI  :  10.1186/s13578-021-00671-9

来源: Springer

【 摘 要 】

BackgroundEpithelial-mesenchymal transition (EMT) and cell stemness are implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Revealing the intrinsic regulatory mechanism may provide effective therapeutic targets for OSCC.ResultsIn this study, we found that Forkhead box D1 (FOXD1) was upregulated in OSCC compared with normal samples. Patients with a higher FOXD1 expression had a poorer overall survival and disease-free survival. Immunohistochemical staining results showed that FOXD1 expression was related to the clinical stage and relapse status of OSCC patients. When FOXD1 expression was knocked down in CAL27 and SCC25 cells, the migration, invasion, colony formation, sphere formation, and proliferation abilities decreased. Moreover, EMT and stemness-related markers changed remarkably, which indicated that the EMT process and cell stemness were inhibited. Conversely, overexpression of FOXD1 promoted EMT and cell stemness. Further study demonstrated that FOXD1 could bind to the promoter region and activate the transcription of SNAI2. In turn, the elevated SNAI2 affected EMT and cell stemness. An in vivo study showed that FOXD1-overexpressing CAL27 cells possessed a stronger tumorigenic ability.ConclusionsOur findings revealed a novel mechanism in regulating EMT and cell stemness and proposed FOXD1 as a potential marker for the diagnosis and treatment of OSCC.

【 授权许可】

CC BY