Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer
Abstract Chemoresistance poses a critical obstacle in bladder cancer (BCa) treatment, and effective interventions are currently limited. Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPH...
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| Format: | Article |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408599 |
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| author | Minhua Deng Zhaohui Zhou Jiawei Chen Xiangdong Li Zefu Liu Jingwei Ye Wensu Wei Ning Wang Yulu Peng Xin Luo Lijuan Jiang Fangjian Zhou Xianchong Zheng Zhuowei Liu |
| author_facet | Minhua Deng Zhaohui Zhou Jiawei Chen Xiangdong Li Zefu Liu Jingwei Ye Wensu Wei Ning Wang Yulu Peng Xin Luo Lijuan Jiang Fangjian Zhou Xianchong Zheng Zhuowei Liu |
| author_sort | Minhua Deng |
| collection | DOAJ |
| description | Abstract Chemoresistance poses a critical obstacle in bladder cancer (BCa) treatment, and effective interventions are currently limited. Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPHOS during cancer cell chemoresistance remain unclear. This study revealed that the mitochondrial translational activator of cytochrome oxidase subunit 1 (TACO1) is linked to stemness and cisplatin resistance in BCa cells. Mechanistically, mitochondrial TACO1 enhances the translation of the mitochondrial cytochrome c oxidase I (MTCO1), promoting mitochondrial reactive oxygen species (mtROS) by upregulating OXPHOS, consequently driving cancer stemness and cisplatin resistance. Intriguingly, the mitochondrial translocation of TACO1 is mediated by the heat shock protein 90 β (HSP90β), a process that requires circFOXK2 as a scaffold for the TACO1‐HSP90β interaction. The mutations at the binding sites of TACO1‐circFOXK2‐HSP90β disturb the ternary complex and inhibit cancer stemness and cisplatin resistance in BCa cells by suppressing the MTCO1/OXPHOS/mtROS axis. Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response. |
| format | Article |
| id | doaj-art-f59f719cdbea43adb2b66d0efc30b0c3 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-f59f719cdbea43adb2b66d0efc30b0c32025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202408599Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder CancerMinhua Deng0Zhaohui Zhou1Jiawei Chen2Xiangdong Li3Zefu Liu4Jingwei Ye5Wensu Wei6Ning Wang7Yulu Peng8Xin Luo9Lijuan Jiang10Fangjian Zhou11Xianchong Zheng12Zhuowei Liu13State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 ChinaAbstract Chemoresistance poses a critical obstacle in bladder cancer (BCa) treatment, and effective interventions are currently limited. Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPHOS during cancer cell chemoresistance remain unclear. This study revealed that the mitochondrial translational activator of cytochrome oxidase subunit 1 (TACO1) is linked to stemness and cisplatin resistance in BCa cells. Mechanistically, mitochondrial TACO1 enhances the translation of the mitochondrial cytochrome c oxidase I (MTCO1), promoting mitochondrial reactive oxygen species (mtROS) by upregulating OXPHOS, consequently driving cancer stemness and cisplatin resistance. Intriguingly, the mitochondrial translocation of TACO1 is mediated by the heat shock protein 90 β (HSP90β), a process that requires circFOXK2 as a scaffold for the TACO1‐HSP90β interaction. The mutations at the binding sites of TACO1‐circFOXK2‐HSP90β disturb the ternary complex and inhibit cancer stemness and cisplatin resistance in BCa cells by suppressing the MTCO1/OXPHOS/mtROS axis. Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response.https://doi.org/10.1002/advs.202408599bladder cancercancer stemnesschemoresistanceoxidative phosphorylationTACO1 |
| spellingShingle | Minhua Deng Zhaohui Zhou Jiawei Chen Xiangdong Li Zefu Liu Jingwei Ye Wensu Wei Ning Wang Yulu Peng Xin Luo Lijuan Jiang Fangjian Zhou Xianchong Zheng Zhuowei Liu Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer Advanced Science bladder cancer cancer stemness chemoresistance oxidative phosphorylation TACO1 |
| title | Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer |
| title_full | Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer |
| title_fullStr | Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer |
| title_full_unstemmed | Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer |
| title_short | Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer |
| title_sort | enhanced oxidative phosphorylation driven by taco1 mitochondrial translocation promotes stemness and cisplatin resistance in bladder cancer |
| topic | bladder cancer cancer stemness chemoresistance oxidative phosphorylation TACO1 |
| url | https://doi.org/10.1002/advs.202408599 |
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