Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis
Abstract Sunitinib is one of the first‐line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src‐associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-10-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4743 |
| _version_ | 1798021929805807616 |
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| author | Zeshen Wu Yulu Peng Longbin Xiong Jun Wang Zhen Li Kang Ning Minhua Deng Ning Wang Wensu Wei Zhiyong Li Pei Dong Chunping Yu Fangjian Zhou Zhiling Zhang |
| author_facet | Zeshen Wu Yulu Peng Longbin Xiong Jun Wang Zhen Li Kang Ning Minhua Deng Ning Wang Wensu Wei Zhiyong Li Pei Dong Chunping Yu Fangjian Zhou Zhiling Zhang |
| author_sort | Zeshen Wu |
| collection | DOAJ |
| description | Abstract Sunitinib is one of the first‐line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src‐associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration‐dependent manner and inhibited the expression of total and phosphorylated Sam68 (p‐Sam68). Downregulation of Sam68 expression inhibited RCC cell apoptosis induced by sunitinib. While upregulation of Sam68 expression could enhance apoptosis induced by sunitinib. Xenograft models showed that tumors in the Sam68‐knockdown group did not shrink as much as those in the control group after treatment with sunitinib for 4 weeks. Together, our results suggest that Sam68 expression is associated with the sensitivity of ccRCC patients to sunitinib. Sam68 may promote cell apoptosis induced by sunitinib, and the Sam68 expression level may be a biomarker for predicting sunitinib sensitivity in ccRCC patients. |
| first_indexed | 2024-04-11T17:21:30Z |
| format | Article |
| id | doaj.art-c2a28f99e24840dca26deb11cf889c05 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-11T17:21:30Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-c2a28f99e24840dca26deb11cf889c052022-12-22T04:12:28ZengWileyCancer Medicine2045-76342022-10-0111193674368610.1002/cam4.4743Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosisZeshen Wu0Yulu Peng1Longbin Xiong2Jun Wang3Zhen Li4Kang Ning5Minhua Deng6Ning Wang7Wensu Wei8Zhiyong Li9Pei Dong10Chunping Yu11Fangjian Zhou12Zhiling Zhang13Department of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou ChinaAbstract Sunitinib is one of the first‐line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src‐associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration‐dependent manner and inhibited the expression of total and phosphorylated Sam68 (p‐Sam68). Downregulation of Sam68 expression inhibited RCC cell apoptosis induced by sunitinib. While upregulation of Sam68 expression could enhance apoptosis induced by sunitinib. Xenograft models showed that tumors in the Sam68‐knockdown group did not shrink as much as those in the control group after treatment with sunitinib for 4 weeks. Together, our results suggest that Sam68 expression is associated with the sensitivity of ccRCC patients to sunitinib. Sam68 may promote cell apoptosis induced by sunitinib, and the Sam68 expression level may be a biomarker for predicting sunitinib sensitivity in ccRCC patients.https://doi.org/10.1002/cam4.4743cell apoptosisdrug sensitivityrenal cell carcinomaSam68sunitinib |
| spellingShingle | Zeshen Wu Yulu Peng Longbin Xiong Jun Wang Zhen Li Kang Ning Minhua Deng Ning Wang Wensu Wei Zhiyong Li Pei Dong Chunping Yu Fangjian Zhou Zhiling Zhang Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis Cancer Medicine cell apoptosis drug sensitivity renal cell carcinoma Sam68 sunitinib |
| title | Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis |
| title_full | Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis |
| title_fullStr | Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis |
| title_full_unstemmed | Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis |
| title_short | Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis |
| title_sort | role of sam68 in sunitinib induced renal cell carcinoma apoptosis |
| topic | cell apoptosis drug sensitivity renal cell carcinoma Sam68 sunitinib |
| url | https://doi.org/10.1002/cam4.4743 |
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