IGF1R Induces ROS Formation in Mitochondria via MICU1 Leads to the Enzalutamide Resistance in Prostate Cancer
- 1Department of Urology The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China
- 2Tianjin Institute of Urology The Second Hospital of Tianjin Medical University Tianjin China
Abstract
After undergoing ADT treatment, drug resistance has emerged as a major hindrance in the treatment of prostate cancer, with enzalutamide resistance being the most notable. Our objective was to identify a new drug‐resistance mechanism present in post‐ADT‐treatment patients. Utilizing proteomic sequencing, we discovered abnormal increases in IGF1R levels. Subsequent sequencing and bioinformatic analyses showed that IGF1R could cause abnormal changes in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation. This phenomenon may be due to IGF1R's influence on the distribution of mitochondrial Ca2+ and the production of reactive oxygen species (ROS). Our CHIP and dual‐luciferase experiments confirmed the regulatory relationship between IGF1R and MICU1. The fluorescent results of Ca2+ and ROS also confirmed that IGF1R could regulate mitochondrial Ca2+ distribution and ROS production. Our team validated the relationship between IGF1R and drug resistance through cell phenotype experiments, and explored its potential as a therapeutic target through a fa‐ci curve. Finally, we verified the effectiveness of the mechanisms we found through a xenograft assay. Our study confirms the potential for IGF1R as a clinical therapeutic target.
Related
- Skin‐Related Adverse Events in Patients Treated With Apalutamide Versus Enzalutamide for Prostate Cancer: A Japanese Real‐World Database Study (A Retrospective Cohort Study)
- Real‐World Overall Survival With Abiraterone Acetate and Enzalutamide in Patients With Chemotherapy‐Naïve Metastatic Castration‐Resistant Prostate Cancer From the Flatiron Electronic Health Records Database
- Cost-effectiveness of adding enzalutamide vs standard non-steroidal antiandrogen drugs for patients with metastatic hormone-sensitive prostate cancer undergoing standard first-line therapy: a within-trial, secondary end-point analysis of the ENZAMET phase 3, international randomized trial (ANZUP 1304)
- Multi-omic profiling reveals metabolic vulnerabilities in enzalutamide resistant prostate cancer.
- Tumor-targeted nanobubbles delivering PFP/siFGFR1 for US imaging and overcoming enzalutamide-resistant in prostate cancer
BibTeX
@article{li2026igf1r,
title = {{IGF1R Induces ROS Formation in Mitochondria via MICU1 Leads to the Enzalutamide Resistance in Prostate Cancer}},
author = {Hanlin Li and Yutong Chen and Yupeng Zhou and Yang Li and Yukui Gao and Xuanrong Chen and Qianwang Ma and Shimiao Zhu and Simeng Wen},
journal = {Journal of Cellular and Molecular Medicine},
year = {2026},
month = oct,
doi = {10.1111/jcmm.71415},
url = {https://doi.org/10.1111/jcmm.71415},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IGF1R Induces ROS Formation in Mitochondria via MICU1 Leads to the Enzalutamide Resistance in Prostate Cancer
AU - Hanlin Li
AU - Yutong Chen
AU - Yupeng Zhou
AU - Yang Li
AU - Yukui Gao
AU - Xuanrong Chen
AU - Qianwang Ma
AU - Shimiao Zhu
AU - Simeng Wen
PY - 2026
DA - 2026/10/27
JO - Journal of Cellular and Molecular Medicine
DO - 10.1111/jcmm.71415
UR - https://doi.org/10.1111/jcmm.71415
AB - After undergoing ADT treatment, drug resistance has emerged as a major hindrance in the treatment of prostate cancer, with enzalutamide resistance being the most notable. Our objective was to identify a new drug‐resistance mechanism present in post‐ADT‐treatment patients. Utilizing proteomic sequencing, we discovered abnormal increases in IGF1R levels. Subsequent sequencing and bioinformatic analyses showed that IGF1R could cause abnormal changes in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation. This phenomenon may be due to IGF1R's influence on the distribution of mitochondrial Ca2+ and the production of reactive oxygen species (ROS). Our CHIP and dual‐luciferase experiments confirmed the regulatory relationship between IGF1R and MICU1. The fluorescent results of Ca2+ and ROS also confirmed that IGF1R could regulate mitochondrial Ca2+ distribution and ROS production. Our team validated the relationship between IGF1R and drug resistance through cell phenotype experiments, and explored its potential as a therapeutic target through a fa‐ci curve. Finally, we verified the effectiveness of the mechanisms we found through a xenograft assay. Our study confirms the potential for IGF1R as a clinical therapeutic target.
SN - 1582-1838
SN - 1582-4934
ER -