Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8
Abstract Background SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. Methods Protein expression was measured with Western blotting, immunohistochemistry or...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1146-7 |
| _version_ | 1818611066471448576 |
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| author | Junwei Huang Eoon Hye Ji Xinyuan Zhao Li Cui Kaori Misuno Mian Guo Zhigang Huang Xiaohong Chen Shen Hu |
| author_facet | Junwei Huang Eoon Hye Ji Xinyuan Zhao Li Cui Kaori Misuno Mian Guo Zhigang Huang Xiaohong Chen Shen Hu |
| author_sort | Junwei Huang |
| collection | DOAJ |
| description | Abstract Background SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. Methods Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays. Results SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells. Conclusion Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8. |
| first_indexed | 2024-12-16T15:24:25Z |
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| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-16T15:24:25Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-6b47504462724437a7288cd9c786e6752022-12-21T22:26:33ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-03-0138111310.1186/s13046-019-1146-7Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8Junwei Huang0Eoon Hye Ji1Xinyuan Zhao2Li Cui3Kaori Misuno4Mian Guo5Zhigang Huang6Xiaohong Chen7Shen Hu8School of Dentistry, University of CaliforniaSchool of Dentistry, University of CaliforniaDepartment of Endodontics, Stomatological Hospital, Southern Medical UniversitySchool of Dentistry, University of CaliforniaSchool of Dentistry, University of CaliforniaSchool of Dentistry, University of CaliforniaDepartment of Otorhinolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Otorhinolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical UniversitySchool of Dentistry, University of CaliforniaAbstract Background SOX11 is a transcription factor that plays an important role in mantle cell lymphoma development. However, its functional role in head and neck squamous cell carcinoma (HNSCC) remains unknown. Methods Protein expression was measured with Western blotting, immunohistochemistry or quantitative proteomics, and gene expression was measured with quantitative RT-PCR. Functional role of SOX11 in HNSCC was evaluated with MTS/apoptosis, migration, invasion assays and a xenograft model. A SOX11-targeting gene, SDCCAG8, was confirmed with chromatin immunoprecipitation (ChIP), luciferase reporter and rescue assays. Results SOX11 was up-regulated in recurrent versus primary HNSCC and in highly invasive versus low invasive HNSCC cell lines. Silencing SOX11 in HNSCC cell lines significantly inhibited the cell proliferation, migration, invasion and resistance to Cisplatin, and vice versa. Quantitative proteomic analysis of SOX11-silencing HNSCC cells revealed a number of differentially expressed proteins, including a down-regulated tumor antigen SDCCAG8. Silencing of SDCCAG8 in HNSCC cells also significantly inhibited the cell proliferation, migration and invasion, and vice versa. ChIP assays demonstrated that endogenous SOX11 strongly bound to Sdccag8 gene promoter in highly invasive HNSCC cells. When over-expressed in low invasive HNSCC cells, wild type SOX11 but not mutant SOX11 induced the promoter activity of Sdccag8 and significantly induced the expression of SDCCAG8. However, exogenous mutant SOX11 abolished the expression of SDCCAG8 in highly invasive HNSCC cells. In addition, the inhibitory effects of SOX11 knockdown were partially rescued by over-expression of SDCCAG8 in HNSCC cells. Conclusion Collectively, our findings indicate SOX11 promotes HNSCC progression via the regulation of SDCCAG8.http://link.springer.com/article/10.1186/s13046-019-1146-7Head and neck squamous cell carcinomaSOX11SDCCAG8ProteomicsInvasion |
| spellingShingle | Junwei Huang Eoon Hye Ji Xinyuan Zhao Li Cui Kaori Misuno Mian Guo Zhigang Huang Xiaohong Chen Shen Hu Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 Journal of Experimental & Clinical Cancer Research Head and neck squamous cell carcinoma SOX11 SDCCAG8 Proteomics Invasion |
| title | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
| title_full | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
| title_fullStr | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
| title_full_unstemmed | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
| title_short | Sox11 promotes head and neck cancer progression via the regulation of SDCCAG8 |
| title_sort | sox11 promotes head and neck cancer progression via the regulation of sdccag8 |
| topic | Head and neck squamous cell carcinoma SOX11 SDCCAG8 Proteomics Invasion |
| url | http://link.springer.com/article/10.1186/s13046-019-1146-7 |
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