E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance
Abstract Oral squamous cell carcinoma (OSCC) is a frequently occurring neck and head malignancy. Therapies for OSCC are improving, but radiotherapy resistance remains a major clinical challenge. Here, we found that the S-phase kinase-associated protein 2 (Skp2) is overexpressed in OSCC cells and tis...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02463-3 |
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| _version_ | 1850201599656329216 |
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| author | Shiming Tan Ruirui Wang Jinglin Fang Ming Yi Pengfei Guo Shuangze Han Xiaoying Li Yu Gan Jinzhuang Liao Xinfang Yu Wei Li |
| author_facet | Shiming Tan Ruirui Wang Jinglin Fang Ming Yi Pengfei Guo Shuangze Han Xiaoying Li Yu Gan Jinzhuang Liao Xinfang Yu Wei Li |
| author_sort | Shiming Tan |
| collection | DOAJ |
| description | Abstract Oral squamous cell carcinoma (OSCC) is a frequently occurring neck and head malignancy. Therapies for OSCC are improving, but radiotherapy resistance remains a major clinical challenge. Here, we found that the S-phase kinase-associated protein 2 (Skp2) is overexpressed in OSCC cells and tissues. Knockdown of Skp2 significantly increased the radiotherapy sensitivity of OSCC cells. Further potential mechanisms suggest that Skp2-deficient restoration of radiotherapy sensitivity in OSCC cells may induce intrinsic apoptosis through inhibition of the Akt/Wee1/CDK1 axis, which inhibits Survivin phosphorylation and promotes its ubiquitination and degradation by FBXL7. Clinicopathologic histological analysis showed that Skp2 was positively correlated with the expression of p-Akt and Survivin in OSCC tissues. Furthermore, knockdown or inhibition of Skp2 overcame the radiotherapy resistance of OSCC cells. In conclusion, our study demonstrated that targeting the Skp2-Survivin axis could serve as an attractive and promising potential therapeutic target for radiotherapy sensitization in OSCC. |
| format | Article |
| id | doaj-art-d062c2c0b9cc4c148ed96c21c8977c8c |
| institution | OA Journals |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-d062c2c0b9cc4c148ed96c21c8977c8c2025-08-20T02:11:58ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111510.1038/s41420-025-02463-3E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistanceShiming Tan0Ruirui Wang1Jinglin Fang2Ming Yi3Pengfei Guo4Shuangze Han5Xiaoying Li6Yu Gan7Jinzhuang Liao8Xinfang Yu9Wei Li10Department of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversitySchool of Stomatology Hunan University of Chinese MedicineDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, XiangYa Hospital, Central South UniversityDepartment of Radiology, The Third Xiangya Hospital of Central South UniversityAbstract Oral squamous cell carcinoma (OSCC) is a frequently occurring neck and head malignancy. Therapies for OSCC are improving, but radiotherapy resistance remains a major clinical challenge. Here, we found that the S-phase kinase-associated protein 2 (Skp2) is overexpressed in OSCC cells and tissues. Knockdown of Skp2 significantly increased the radiotherapy sensitivity of OSCC cells. Further potential mechanisms suggest that Skp2-deficient restoration of radiotherapy sensitivity in OSCC cells may induce intrinsic apoptosis through inhibition of the Akt/Wee1/CDK1 axis, which inhibits Survivin phosphorylation and promotes its ubiquitination and degradation by FBXL7. Clinicopathologic histological analysis showed that Skp2 was positively correlated with the expression of p-Akt and Survivin in OSCC tissues. Furthermore, knockdown or inhibition of Skp2 overcame the radiotherapy resistance of OSCC cells. In conclusion, our study demonstrated that targeting the Skp2-Survivin axis could serve as an attractive and promising potential therapeutic target for radiotherapy sensitization in OSCC.https://doi.org/10.1038/s41420-025-02463-3 |
| spellingShingle | Shiming Tan Ruirui Wang Jinglin Fang Ming Yi Pengfei Guo Shuangze Han Xiaoying Li Yu Gan Jinzhuang Liao Xinfang Yu Wei Li E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance Cell Death Discovery |
| title | E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance |
| title_full | E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance |
| title_fullStr | E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance |
| title_full_unstemmed | E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance |
| title_short | E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance |
| title_sort | e3 ligase skp2 mediated stabilization of survivin contributes to radioresistance |
| url | https://doi.org/10.1038/s41420-025-02463-3 |
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