FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2
Abstract Background 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. Results In this study, we found that...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-021-00671-9 |
| _version_ | 1818608910232190976 |
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| author | Yang Chen Weilian Liang Ke Liu Zhengjun Shang |
| author_facet | Yang Chen Weilian Liang Ke Liu Zhengjun Shang |
| author_sort | Yang Chen |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-16T14:50:09Z |
| format | Article |
| id | doaj.art-ce63d1cf766d4f0a85c435aa22b15077 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-16T14:50:09Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-ce63d1cf766d4f0a85c435aa22b150772022-12-21T22:27:37ZengBMCCell & Bioscience2045-37012021-08-0111111410.1186/s13578-021-00671-9FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2Yang Chen0Weilian Liang1Ke Liu2Zhengjun Shang3The 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)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)Department of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan UniversityDepartment of Oral and Maxillofacial-Head and Neck Oncology, School and Hospital of Stomatology, Wuhan UniversityAbstract Background 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13578-021-00671-9FOXD1EMTSTEMNESSSNAI2OSCC |
| spellingShingle | Yang Chen Weilian Liang Ke Liu Zhengjun Shang FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 Cell & Bioscience FOXD1 EMT STEMNESS SNAI2 OSCC |
| title | FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 |
| title_full | FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 |
| title_fullStr | FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 |
| title_full_unstemmed | FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 |
| title_short | FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2 |
| title_sort | foxd1 promotes emt and cell stemness of oral squamous cell carcinoma by transcriptional activation of snai2 |
| topic | FOXD1 EMT STEMNESS SNAI2 OSCC |
| url | https://doi.org/10.1186/s13578-021-00671-9 |
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