文章：

G蛋白偶联雌激素受体激活诱导p53与ADAMTS1表达抑制肿瘤生长并抑制肝癌转移

Activation of G Protein-Coupled Estrogen Receptor Induces p53 and ADAMTS1 to Inhibit Tumor Growth and Suppress Liver Cancer Metastasis

原文发布日期：11 August 2025

DOI: 10.3390/cancers17162623

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Liver cancer is a common cause of cancer-related deaths among men and women globally. A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMST1) has been associated with various cancers, including prostate, esophageal, renal, and breast cancers. However, its role in liver cancer remains unclear. The aim of this study was to investigate the relationship between G protein-coupled estrogen (GPER) activation via its agonist, G1, and ADAMTS1 in suppressing liver cancer metastasis.Methods: Following preliminary assessment of Hep3B, Huh7, and SK-Hep-1 cells, SK-Hep-1 cells were selected owing to their elevated GPER expression and reduced cell viability. Cells were subjected to flow cytometry, RNA sequencing, and proteomics analyses. We established an SK-Hep-1 xenograft model for in vivo analysis.Results: We observed G1-induced G2-M phase cell cycle arrest, increased p53 and p21, and decreased cell cycle-related factors. In vivo, G1 significantly inhibited tumor growth and increased p53 protein expression. ADAMTS1, a metastasis regulator, was significantly upregulated by G1. G1 reduced the proliferating cell nuclear antigen and increased E-cadherin expression in SK-Hep-1 cells and in vivo. Tumor invasion was reduced with G1 and ADAMTS1 expression. In vivo, G1 reduced liver metastasis, increased E-cadherin, and decreased vimentin and proliferating cell nuclear antigen in primary tumor tissues and increased ADAMTS1 at the tumor edge.Conclusions: GPER agonists, such as G1, show potential for suppressing liver cancer progression and metastasis.

摘要翻译： 

背景/目的：肝癌是全球范围内男性和女性癌症相关死亡的常见原因。含血小板反应蛋白基序的解整合素金属蛋白酶1（ADAMTS1）已被证实与多种癌症相关，包括前列腺癌、食管癌、肾癌和乳腺癌。然而，其在肝癌中的作用尚不明确。本研究旨在探讨通过其激动剂G1激活G蛋白偶联雌激素受体（GPER）与ADAMTS1在抑制肝癌转移中的关系。 方法：在对Hep3B、Huh7和SK-Hep-1细胞进行初步评估后，选择SK-Hep-1细胞进行后续研究，因其GPER表达较高且细胞活力较低。对细胞进行流式细胞术、RNA测序和蛋白质组学分析。建立SK-Hep-1异种移植模型用于体内分析。 结果：我们观察到G1诱导G2-M期细胞周期阻滞，增加p53和p21表达，并降低细胞周期相关因子水平。在体内实验中，G1显著抑制肿瘤生长并增加p53蛋白表达。转移调节因子ADAMTS1在G1作用下显著上调。G1在SK-Hep-1细胞及体内模型中降低增殖细胞核抗原表达，同时增加E-钙黏蛋白表达。G1与ADAMTS1表达共同抑制肿瘤侵袭。在体内实验中，G1减少肝转移，在原发肿瘤组织中增加E-钙黏蛋白、降低波形蛋白和增殖细胞核抗原表达，并在肿瘤边缘增加ADAMTS1表达。 结论：GPER激动剂（如G1）在抑制肝癌进展和转移方面显示出潜在应用价值。

原文链接：

Activation of G Protein-Coupled Estrogen Receptor Induces p53 and ADAMTS1 to Inhibit Tumor Growth and Suppress Liver Cancer Metastasis