cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells
Cyclic GMP-AMP synthase (cGAS) plays an important role in biological responses to pathogens. The activation of the cGAS pathway in immune cells is known to induce antitumor effects, but the role of cGAS in cancer cells remains poorly understood. In silico analysis using public databases suggested th...
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1434 |
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| author | Taichi Nyui Hironori Yoshino Tetsuya Nunota Yoshiaki Sato Eichi Tsuruga |
| author_facet | Taichi Nyui Hironori Yoshino Tetsuya Nunota Yoshiaki Sato Eichi Tsuruga |
| author_sort | Taichi Nyui |
| collection | DOAJ |
| description | Cyclic GMP-AMP synthase (cGAS) plays an important role in biological responses to pathogens. The activation of the cGAS pathway in immune cells is known to induce antitumor effects, but the role of cGAS in cancer cells remains poorly understood. In silico analysis using public databases suggested that high cGAS expression in head and neck squamous cell carcinoma (HNSCC) is indicative of a poor prognosis for HNSCC patients. We therefore investigated the role of cGAS in malignancies and the cellular radiation response of human HNSCC cells (SAS and Ca9-22) in vitro, because radiotherapy is one of the treatments most commonly used for HNSCC. Although cGAS knockdown failed to suppress the proliferation of non-irradiated HNSCC cells, it enhanced the radiosensitivity of HNSCC cells. The administration of the cGAS agonist increased the radioresistance of HNSCC cells. cGAS knockdown increased radiation-induced mitotic catastrophe, apoptosis, or cellular senescence, depending on the cell line, and this cell line-dependent response might be due to different responses of p21 after irradiation. Collectively, our findings indicate that the cGAS pathway regulates the radioresistance of HNSCC cells. |
| first_indexed | 2024-03-10T04:17:17Z |
| format | Article |
| id | doaj.art-b820d7005e1040c4b3f895dfd6f4754d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:17:17Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b820d7005e1040c4b3f895dfd6f4754d2023-11-23T07:59:11ZengMDPI AGCells2073-44092022-04-01119143410.3390/cells11091434cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma CellsTaichi Nyui0Hironori Yoshino1Tetsuya Nunota2Yoshiaki Sato3Eichi Tsuruga4Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Aomori, JapanDepartment of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Aomori, JapanDepartment of Radiological Technology, Hirosaki University School of Health Sciences, Hirosaki 036-8564, Aomori, JapanDepartment of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Aomori, JapanDepartment of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Aomori, JapanCyclic GMP-AMP synthase (cGAS) plays an important role in biological responses to pathogens. The activation of the cGAS pathway in immune cells is known to induce antitumor effects, but the role of cGAS in cancer cells remains poorly understood. In silico analysis using public databases suggested that high cGAS expression in head and neck squamous cell carcinoma (HNSCC) is indicative of a poor prognosis for HNSCC patients. We therefore investigated the role of cGAS in malignancies and the cellular radiation response of human HNSCC cells (SAS and Ca9-22) in vitro, because radiotherapy is one of the treatments most commonly used for HNSCC. Although cGAS knockdown failed to suppress the proliferation of non-irradiated HNSCC cells, it enhanced the radiosensitivity of HNSCC cells. The administration of the cGAS agonist increased the radioresistance of HNSCC cells. cGAS knockdown increased radiation-induced mitotic catastrophe, apoptosis, or cellular senescence, depending on the cell line, and this cell line-dependent response might be due to different responses of p21 after irradiation. Collectively, our findings indicate that the cGAS pathway regulates the radioresistance of HNSCC cells.https://www.mdpi.com/2073-4409/11/9/1434cyclic GMP-AMP synthasehead and neck squamous cell carcinomaradiosensitivityapoptosismitotic catastrophecellular senescence |
| spellingShingle | Taichi Nyui Hironori Yoshino Tetsuya Nunota Yoshiaki Sato Eichi Tsuruga cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells Cells cyclic GMP-AMP synthase head and neck squamous cell carcinoma radiosensitivity apoptosis mitotic catastrophe cellular senescence |
| title | cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells |
| title_full | cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells |
| title_fullStr | cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells |
| title_full_unstemmed | cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells |
| title_short | cGAS Regulates the Radioresistance of Human Head and Neck Squamous Cell Carcinoma Cells |
| title_sort | cgas regulates the radioresistance of human head and neck squamous cell carcinoma cells |
| topic | cyclic GMP-AMP synthase head and neck squamous cell carcinoma radiosensitivity apoptosis mitotic catastrophe cellular senescence |
| url | https://www.mdpi.com/2073-4409/11/9/1434 |
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