TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer
Abstract Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta‐like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202400160 |
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| author | Xiuqing Lu Chao Zhang Lewei Zhu Sifen Wang Lijun Zeng Wenjing Zhong Xuxia Wu Qi Yuan Hailin Tang Shien Cui Yeru Tan Yuehua Li Weidong Wei |
| author_facet | Xiuqing Lu Chao Zhang Lewei Zhu Sifen Wang Lijun Zeng Wenjing Zhong Xuxia Wu Qi Yuan Hailin Tang Shien Cui Yeru Tan Yuehua Li Weidong Wei |
| author_sort | Xiuqing Lu |
| collection | DOAJ |
| description | Abstract Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta‐like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is analyzed using real‐time PCR, western blotting, and immunohistochemistry in BC patient specimens. Kaplan–Meier survival analysis is employed to assess its prognostic significance. Proteomic analysis, immunoprecipitation tests, and protein immunoblotting are employed to examine the impact of TBL2 on AKT phosphorylation activation. The findings reveal selective overexpression of TBL2 in BC, correlating significantly with various clinicopathological characteristics and poor survival outcomes in patients with BC. Through in vivo and in vitro experiments, it is observed that TBL2 suppression inhibits BC cell proliferation, while TBL2 overexpression has the opposite effect. Mechanistically, TBL2 is identified as a scaffolding protein that promotes PRMT5 and WDR77 interaction. This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment. |
| format | Article |
| id | doaj-art-60f8922a631346529072cf07536e6786 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-60f8922a631346529072cf07536e67862025-08-20T01:58:42ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202400160TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast CancerXiuqing Lu0Chao Zhang1Lewei Zhu2Sifen Wang3Lijun Zeng4Wenjing Zhong5Xuxia Wu6Qi Yuan7Hailin Tang8Shien Cui9Yeru Tan10Yuehua Li11Weidong Wei12State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaDepartment of Breast Surgery The First People's Hospital of Foshan Foshan Guangdong 528000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaThe First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaDistrict 2 Breast Center Zhongshan City People's Hospital Zhongshan 528400 ChinaThe First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510000 ChinaAbstract Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta‐like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is analyzed using real‐time PCR, western blotting, and immunohistochemistry in BC patient specimens. Kaplan–Meier survival analysis is employed to assess its prognostic significance. Proteomic analysis, immunoprecipitation tests, and protein immunoblotting are employed to examine the impact of TBL2 on AKT phosphorylation activation. The findings reveal selective overexpression of TBL2 in BC, correlating significantly with various clinicopathological characteristics and poor survival outcomes in patients with BC. Through in vivo and in vitro experiments, it is observed that TBL2 suppression inhibits BC cell proliferation, while TBL2 overexpression has the opposite effect. Mechanistically, TBL2 is identified as a scaffolding protein that promotes PRMT5 and WDR77 interaction. This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment.https://doi.org/10.1002/advs.202400160AKT phosphorylationbreast cancerPRMT5/WDR77proliferationTBL2 |
| spellingShingle | Xiuqing Lu Chao Zhang Lewei Zhu Sifen Wang Lijun Zeng Wenjing Zhong Xuxia Wu Qi Yuan Hailin Tang Shien Cui Yeru Tan Yuehua Li Weidong Wei TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer Advanced Science AKT phosphorylation breast cancer PRMT5/WDR77 proliferation TBL2 |
| title | TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer |
| title_full | TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer |
| title_fullStr | TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer |
| title_full_unstemmed | TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer |
| title_short | TBL2 Promotes Tumorigenesis via PRMT5/WDR77‐Mediated AKT Activation in Breast Cancer |
| title_sort | tbl2 promotes tumorigenesis via prmt5 wdr77 mediated akt activation in breast cancer |
| topic | AKT phosphorylation breast cancer PRMT5/WDR77 proliferation TBL2 |
| url | https://doi.org/10.1002/advs.202400160 |
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