FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2.
FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2.
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FOXD1通过转录激活SNAI2促进口腔鳞状细胞癌的EMT和细胞干细胞性
DOI：
10.1186/s13578-021-00671-9
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发表时间：
2021-08-04
影响因子：
7.5
通讯作者：
Shang Z
中科院分区：
文献类型：
--
作者：
Chen Y;Liang W;Liu K;Shang Z
上皮-间充质转化(EMT)和细胞干性与口腔鳞状细胞癌(OSCC)的发生和发展有关。揭示口腔鳞癌的内在调控机制可能为口腔鳞癌提供有效的治疗靶点。在本研究中，我们发现与正常口腔鳞癌组织相比，口腔鳞癌组织中Forkhead box D1(FOXD1)基因表达上调。FOXD1高表达的患者总体生存期和无瘤生存期较差。免疫组织化学染色结果显示，FOXD1的表达与口腔鳞癌患者的临床分期和复发状态有关。当FOXD1在CAL27和SCC25细胞中表达下调时，细胞的迁移、侵袭、集落形成、球体形成和增殖能力下降。此外，EMT和茎性相关标记发生了显著变化，表明EMT过程和细胞干性受到抑制。相反，FOXD1的过表达促进了EMT和细胞干化。进一步研究表明，FOXD1能与SNAI2启动子结合，激活SNAI2的转录。反过来，升高的SNAI2影响EMT和细胞干性。体内研究表明，高表达FOXD1的CAL27细胞具有较强的致瘤能力。我们的发现揭示了一种新的调节EMT和细胞干性的机制，并建议FOXD1作为口腔鳞癌诊断和治疗的潜在标记物。网上版载有补充材料，可在10.1186/s13578-021-00671-9查阅。
Epithelial-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. In 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. Our 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. The online version contains supplementary material available at 10.1186/s13578-021-00671-9.
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影响因子：
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