ArticleFrontiers in oncology2021
GPER-Induced ERK Signaling Decreases Cell Viability of Hepatocellular Carcinoma.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Molecular mechanisms of sex hormones in Hepatocellular Carcinoma: a systematic review.Molecular biology reports · 2025Pooled it
- Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.Cancer biology & medicine · 2024Pooled it
- Estradiol mitigates lipid accumulation, oxidative stress, apoptosis, and MAPKs activation in NASH rat model with bilateral orchidectomy.PNAS nexus · 2026Article
- Sexual dimorphism in the liver.Nature reviews. Gastroenterology & hepatology · 2026Review
- Overexpression of GPER1 suppressed esophageal carcinoma growthEuropean journal of histochemistry : EJH · 2026Article
- GPER in metabolic homeostasis and disease: molecular mechanisms, nutritional regulation, and therapeutic potential.Journal of translational medicine · 2025Review
- Article
- PGRP-S promotes hepatocellular carcinoma progression via MAPK/ERK pathway by interaction with TTC1.Scientific reports · 2025Article
- Effects of atrazine on the HPG and HPA axes and steroidogenic pathways in females: relevance to reproductive function and breast, ovarian and uterine cancer.Frontiers in toxicology · 2025Review
- Article
- GPER1 signaling restricts macrophage proliferation and accumulation in human hepatocellular carcinoma.Frontiers in immunology · 2024Article
- GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments.International journal of molecular sciences · 2023Review
- LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway.Cancer research communications · 2023Article
- Review
- NLRP3 inflammasome activation By 17β-estradiol is a potential therapeutic target in hepatocellular carcinoma treatment.Medical oncology (Northwood, London, England) · 2023Article
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- Targeted activation of GPER enhances the efficacy of venetoclax by boosting leukemic pyroptosis and CD8+ T cell immune function in acute myeloid leukemia.Cell death & disease · 2022Article
- Assessment of G Protein-Coupled Oestrogen Receptor Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody.International journal of molecular sciences · 2022Article
- Therapeutic Value of Estrogen Receptor α in Hepatocellular Carcinoma Based on Molecular Mechanisms.Journal of clinical and translational hepatology · 2022Review
- Hepatocellular Carcinoma: Current Therapeutic Algorithm for Localized and Advanced Disease.Journal of oncology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Effective biomarkers and specific therapeutic targets for HCC are therefore urgently needed. G protein-coupled estrogen receptor (GPER) plays a crucial role in numerous cancer types; however, its functions in HCC require further exploration. In the present study, we found a remarkable difference in GPER staining between tumor tissue (100/141, 70.9%) and matched non-tumor tissue (27/30, 90.0%). Compared with the GPER-negative patients, the GPER-positive patients with HCC were closely associated with female sex, negative hepatitis B surface antigen, small tumor size, low serum alpha fetoprotein level, and longer overall survival. Treatment with GPER-specific agonist G1 led to the sustained and transient activation of the EGFR/ERK and EGFR/AKT signaling pathways, respectively, in the HCC cell lines HCCLM3 and SMMC-7721, which express high levels of GPER. Interestingly, G1-induced EGFR/ERK signaling, rather than EGFR/AKT signaling mediated by GPER, was involved in decreasing cell viability by blocking cell cycle progression, thereby promoting apoptosis and inhibiting cell growth. Clinical analysis indicated that simultaneous high expression of GPER and phosphorylated-ERK (p-ERK) predicted improved prognosis for HCC. Finally, the activation of GPER/ERK signaling remarkably suppressed tumor growth in an HCC xenograft model, and this result was consistent with the
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