Zhou S, Cheng X, Zhang JM, Ji J, Ni ZZ, Wang W. Estrogen receptor 1 regulates ovarian cancer cell stemness and ferroptosis through modulation of the canonical RhoA/ROCK signaling pathway. World J Stem Cells 2026; 18(9): 121744 [DOI: 10.4252/wjsc.121744]
Corresponding Author of This Article
Wei Wang, Department of Pathology, Jiangsu Province Official Hospital, Geriatric Hospital of Nanjing Medical University, No. 65 Jiangsu Road, Nanjing 210009, Jiangsu Province, China. path_lucky@126.com
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Oncology
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research-article
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Zhou S, Cheng X, Zhang JM, Ji J, Ni ZZ, Wang W. Estrogen receptor 1 regulates ovarian cancer cell stemness and ferroptosis through modulation of the canonical RhoA/ROCK signaling pathway. World J Stem Cells 2026; 18(9): 121744 [DOI: 10.4252/wjsc.121744]
World J Stem Cells. Sep 26, 2026; 18(9): 121744 Published online Sep 26, 2026. doi: 10.4252/wjsc.121744
Estrogen receptor 1 regulates ovarian cancer cell stemness and ferroptosis through modulation of the canonical RhoA/ROCK signaling pathway
Shun Zhou, Xue Cheng, Jing-Min Zhang, Jie Ji, Zhen-Zhen Ni, Wei Wang
Shun Zhou, Department of Interventional, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, Jiangsu Province, China
Xue Cheng, Jing-Min Zhang, Jie Ji, Zhen-Zhen Ni, Department of Pathology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, Jiangsu Province, China
Wei Wang, Department of Pathology, Jiangsu Province Official Hospital, Geriatric Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu Province, China
Author contributions: Zhou S and Wang W conceived and designed the study; Cheng X, Zhang JM, Ji J, and Ni ZZ performed data curation, methodology, and software analyses; Zhou S carried out the investigation, formal analysis, visualization, and wrote the original draft of the manuscript; Wang W handled project administration, resource acquisition, supervision, validation, and reviewed and edited the manuscript. All authors approved the final version.
AI contribution statement: No AI tools were used in the manuscript editing, figures, and data analysis.
Supported by the Talent Construction Fund Research Project of Jiangsu Province Geriatric Hospital, No. IR2024101.
Institutional review board statement: Clinical samples and experimental animals are not available in this paper.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw data can be obtained on request from the corresponding author.
Corresponding author: Wei Wang, Department of Pathology, Jiangsu Province Official Hospital, Geriatric Hospital of Nanjing Medical University, No. 65 Jiangsu Road, Nanjing 210009, Jiangsu Province, China. path_lucky@126.com
Received: April 1, 2026 Revised: May 19, 2026 Accepted: August 28, 2026 Published online: September 26, 2026 Processing time: 177 Days and 3.8 Hours
Abstract
BACKGROUND
This study investigated the role of the estrogen receptor 1 (ESR1) in ovarian cancer and its underlying mechanisms. Target genes associated with ovarian cancer, cell stemness, and ferroptosis were identified using DisGeNET and GeneCards databases.
AIM
To explore the effect of ESR1 on ovarian cancer and its potential molecular mechanism.
METHODS
ESR1 expression levels in HOSE, SKOV3, A2780, and OVCAR3 cells were assessed using real-time polymerase chain reaction and western blotting. ESR1 knockdown was performed in A2780 cells to evaluate its effects on cell viability, proliferation, apoptosis, aldehyde dehydrogenase activity, cell stemness, ferroptosis, and the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase (ROCK) signaling pathway with or without treatment with CN03 (a Rho activator).
RESULTS
ESR1, a gene associated with ovarian cancer, cell stemness, and ferroptosis, was significantly upregulated in ovarian cancer cells and interacted with the RhoA/ROCK signaling pathway. ESR1 knockdown resulted in decreased levels of RhoA, ROCK1, and ROCK2, reduced cell viability and proliferation, and increased apoptosis, all of which were reversed by CN03 treatment. Additionally, si-ESR1 led to decreased aldehyde dehydrogenase activity and cell stemness, reduced expression of octamer-binding transcription factor 4 and Nanog, increased Fe2+ levels, and elevated expression of ferritin heavy chain, ferritin light chain, and transferrin receptor 1. These changes were reversed by CN03 treatment.
CONCLUSION
ESR1 inhibition regulates cell stemness and ferroptosis in ovarian cancer by modulating the RhoA/ROCK signaling pathway.
Core Tip: This study investigated the effects of estrogen receptor 1 (ESR1) on ovarian cancer. Our findings revealed that ESR1, an overexpressed gene associated with cell stemness and ferroptosis in ovarian cancer, interacts with the Ras homolog (Rho) gene family member A/Rho-associated coiled-coil containing protein kinase signaling pathway. ESR1 knockdown in A2780 cells significantly decreased cell viability and proliferation, while increasing apoptosis. ESR1 silencing also reduced cell stemness (lowered aldehyde dehydrogenase, octamer-binding transcription factor 4, and Nanog) and promoted ferroptosis (increased Fe2+, ferritin heavy chain, and ferritin light chain, and decreased transferrin receptor 1). These inhibitory effects were reversed by treatment with CN03 (a Rho activator), demonstrating that ESR1 regulates ovarian cancer stemness and ferroptosis via the Ras homolog gene family member A/Rho-associated coiled-coil containing protein kinase signaling pathway.
