肝细胞癌（HCC）是最常见的原发性肝癌。富含亮氨酸重复序列的G蛋白偶联受体4（LGR4）参与肿瘤的进展、侵袭和转移。我们的研究旨在调查LGR4与表皮生长因子受体（EGFR）对HCC细胞的影响。我们采用Hep3B和Huh7细胞进行研究。通过CCK8和Transwell分析来表征细胞的综合生物学活性。使用分子生物学技术确定蛋白质的表达。将Hep3B用于小鼠皮下肿瘤实验。评估肿瘤生长和蛋白质表达水平。LGR4过表达可以促进细胞的增殖、迁移和侵袭能力，而siLGR4和siEGFR则可以抑制细胞的生物活性。此外，LGR4过表达促进了RSPO2、β-catenin、EGFR和癌干细胞（CSCs）标记物的表达水平，而LGR4或EGFR的沉默则可以减少β-catenin和CSCs标记物的表达水平。此外，LGR4或EGFR的沉默也抑制肿瘤生长并降低体内RSPO2、CD133、CD44、Nanog、β-catenin的表达水平。我们的数据表明，在HCC中，LGR4 / EGFR信号通路诱导肿瘤生长，而这又导致干细胞特性。这可能是HCC治疗靶向治疗的新视角。版权所有© 2023 Elsevier Ltd.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Leucine-rich repeat containing G-protein-coupled receptors 4 (LGR4) participates in tumor progression, invasion, and metastasis. Our study aimed to investigate the effect of LGR4 with epidermal growth factor receptor (EGFR) in HCC cells.We employed Hep3B and Huh7 cells to conduct our research. Comprehensive biological activities were characterized by CCK8 and transwell assay. Molecular biology techniques were used to determine the expression of proteins. Hep3B was employed to conduct subcutaneous tumor in mice. The tumor growth and the expression levels of proteins were assessed.LGR4 overexpression could promote the cells proliferation, migration, and invasion ability, while siLGR4 and siEGFR could inhibit cells biological activities. In addition, LGR4 overexpression promoted the expression levels of RSPO2, β-catenin, EGFR and cancer stem cells (CSCs) markers, whereas silence of LGR4 or EGFR could diminish the expression levels of β-catenin and CSCs markers. Furthermore, knockdown of LGR4 or EGFR also inhibited tumor growth and reduced the expression levels of RSPO2, CD133, CD44, Nanog, β-catenin in vivo.Our data suggest that LGR4 /EGFR signaling in HCC leads to induce tumor growth, which then contributes to stem cell characteristics. It maybe a new perspective for the targeted therapy of HCC treatment.Copyright © 2023 Elsevier Ltd. All rights reserved.