ArticleFrontiers in oncology2021
Estrogen Receptor 1 Inhibition of Wnt/β-Catenin Signaling Contributes to Sex Differences in Hepatocarcinogenesis.
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 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 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
- Neonatal diethylstilbestrol exposure disrupts uterine epithelial apical-basal polarity and partial EMT state.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- The potential role of sex related differences of the microbiome and its impact on calcific aortic stenosis: a narrative review.Biology of sex differences · 2026Review
- Circulating miR-184 and miR-206 as predictive biomarkers for early recurrence in HBV-related hepatocellular carcinoma: a prospective study.BMC gastroenterology · 2026Article
- Overcoming the Low Bioavailability of Apigenin: The Therapeutic Efficacy for Androgenetic Alopecia Through Topical Administration.Food science & nutrition · 2025Article
- Association of TP53 with Defective Long Chain 3-Hydroxy acyl-CoA Dehydrogenase Induced Non-Cirrhotic Hepatocellular Carcinoma.Cancers · 2025Article
- Article
- Estrogen receptor α suppresses hepatocellular carcinoma by restricting M2 macrophage infiltration through the YAP-CCL2 axis.BMC cancer · 2025Article
- Review
- Testosterone, β-estradiol, and hepatocellular carcinoma: stimulation or inhibition? A comparative effect analysis on cell cycle, apoptosis, and Wnt signaling of HepG2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities.Genes & diseases · 2024Review
- Bioinformatics and machine learning driven key genes screening for hepatocellular carcinoma.Biochemistry and biophysics reports · 2024Article
- Current Perspectives on the Molecular and Clinical Relationships between Primary Biliary Cholangitis and Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Transcription factors-related molecular subtypes and risk prognostic model: exploring the immunogenicity landscape and potential drug targets in hepatocellular carcinoma.Cancer cell international · 2024Article
- Article
- Gut Microbiome and Hepatic Transcriptomic Determinants of HCC Development in Mice with Metabolic Dysfunction-Associated Steatohepatitis.Journal of hepatocellular carcinoma · 2024Article
- Molecular landscape of kidney allograft tissues data integration portal (NephroDIP): a curated database to improve integration of high-throughput kidney transplant datasets.Frontiers in immunology · 2024Article
- Sex differences in radiation research.International journal of radiation biology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular Carcinoma (HCC) is a sexually dimorphic cancer, with female sex being independently protective against HCC incidence and progression. The aim of our study was to understand the mechanism of estrogen receptor signaling in driving sex differences in hepatocarcinogenesis.
methodsWe integrated 1,268 HCC patient sample profiles from publicly available gene expression data to identify the most differentially expressed genes (DEGs). We mapped DEGs into a physical protein interaction network and performed network topology analysis to identify the most important proteins. Experimental validation was performed
resultsWe showed that the most central protein, ESR1, is HCC prognostic, as increased ESR1 expression was protective for overall survival, with HR=0.45 (95%CI 0.32-0.64, p=4.4E-06), and was more pronounced in women. Transfection of HCC cell lines with ESR1 and exposure to estradiol affected expression of genes involved in the Wnt/β-catenin signaling pathway. ER-α (protein product of ESR1) agonist treatment in a mouse model of HCC resulted in significantly longer survival and decreased tumor burden (p<0.0001), with inhibition of Wnt/β-Catenin signaling.
conclusionCombined, the centrality of ESR1 and its inhibition of the Wnt/β-catenin signaling axis provide a biological rationale for protection against HCC incidence and progression in women.
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