Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2024 Dec 10

PMID 39656941

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Exosome-transmitted LUCAT1 promotes stemness transformation and chemoresistance in bladder cancer by binding to IGF2BP2.

Zhan Y, Zhou Z, Zhu Z, Zhang L, Yu S, Liu Y J Exp Clin Cancer Res. 2025; 44(1):80.

PMID: 40025525 PMC: 11874664. DOI: 10.1186/s13046-025-03330-w.

Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer.

Deng M, Zhou Z, Chen J, Li X, Liu Z, Ye J Adv Sci (Weinh). 2024; 12(5):e2408599.

PMID: 39656941 PMC: 11791945. DOI: 10.1002/advs.202408599.

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