Articles
Vol. 70 No. 1 (2026)
https://doi.org/10.4081/ejh.2026.4422

Overexpression of GPER1 suppressed esophageal carcinoma growth via activating cAMP pathway

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Published: 26 January 2026
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G protein-coupled estrogen receptor 1, ferroptosis, esophageal carcinoma, GPX4

Authors

Hongmei Yin
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei; Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Xiumei Han
Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Qun Zhang
Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Duojie Li
Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Fan Wang
wangfan6682024@163.com
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

G protein-coupled estrogen receptor 1 (GPER1) has extensively verified as a tumor regulator in various types of cancers. However, its role in esophageal cancer (EC) remains largely unclear. In this study, the expression and prognostic prediction value of GPER1 in EC was analyzed by using TCGA database and was verified in EC cells and fresh tissues. The results showed that GPER1 is decreased in EC cells and tissues, and lower GPER1 expression is associated with poor overall survival of EC patients. CCK-8 assay and flow apoptosis cytometry were applied to measure the ability of proliferation and apoptosis of EC cells with or without GPER1 overexpression. The levels of reactive oxygen species (ROS) and Fe2+ were determined by flow cytometry. Elisa and Western blotting were employed to measure the markers of ferroptosis and cyclic adenosine monophosphate (cAMP) pathway. The results of in vitro experiments indicated that overexpression of GPER1 caused decreased proliferation, increased cell apoptosis, ROS generation, Fe2+ content and acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, while decreased glutathione peroxidase 4 (GPX4) expression. Notably, the cAMP/PKA inhibitor H89 significantly reversed the ferroptotic effects induced by GPER1, indicating the essential role of the cAMP pathway in this process. The weight and volumes of tumors were measured and Ki-67 and H&E staining were conducted to analyze the effect of GPER1 in vivo. The results of in vivo experiments indicated that overexpression of GPER1 resulted in restricted tumor growth, reduced Ki-67 expression and increased cell death. In conclusion, the expression of GPER1 is reduced in EC. Overexpression of GPER1 enhances ferroptosis in EC, primarily through activation of the cAMP signaling pathway.

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Ethics Approval

this study was approved by the Clinical Research Ethics Committee of Bengbu Medical University (approval No. 2025-(Lunshen)-541), All animal experiments were approved by the Animal Ethics Committee of Bengbu Medical University (approval No. 2025-(Lunshen)-730)

CRediT authorship contribution

Hongmei Yin, data analysis and interpretation, histological examination, writing- original draft preparation. Xiumei Han, Qun Zhang, Duojie Li, data analysis and interpretation. Fan Wang, histological examination, writing- original draft preparation. All authors read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work.

Data Availability Statement

All data is available upon reasonable request from the corresponding author.

How to Cite



1.
Yin H, Han X, Zhang Q, Li D, Wang F. Overexpression of GPER1 suppressed esophageal carcinoma growth via activating cAMP pathway. Eur J Histochem [Internet]. 2026 Jan. 26 [cited 2026 Jan. 27];70(1). Available from: https://www.ejh.it/ejh/article/view/4422
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