Xia Jie, Chen Ke, Wang Jiaqi, Wang Jing, Fan Yi, Li Qian, Kong Lingjun, You Zhonglan
Institute of Infectious Diseases, Southwest Hospital, Army Medical University, Chongqing, China.
Department of Health Statistics, College of Preventive Medicine, Army Medical University, NO. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Med Oncol. 2024 Dec 19;42(1):33. doi: 10.1007/s12032-024-02585-1.
Hepatocellular carcinoma (HCC) is a highly malignant cancer and lacks effective therapeutic targets. The role of LIM/homeobox protein Lhx3 (LHX3) has been extensively studied in various tumor tissues, where it has been identified as a promoter of tumorigenesis and malignancy. However, the specific functional role and potential mechanism of LHX3 in human HCCs are not clearly clarified. We found that LHX3 was overexpressed in HCC tissues compared to adjacent tissues. Moreover, it was observed that LHX3 promoted the epithelial-mesenchymal transition (EMT) of HCC cells, leading to increased proliferation, migration, and viability, and adhesion ability in vitro. Mechanistically, LHX3 facilitated TCF4 binding to β-catenin, forming a stable LHX3/TCF4/β-catenin complex that activated downstream target genes. Disruption of the β-catenin/TCF4 interaction by Toxoflavin prevented the EMT of HCC cells. Overall, these findings highlight the critical role of LHX3 in the EMT of HCC cells through the β-catenin/TCF4 axis, suggesting the LHX3/β-catenin/TCF4 axis as a potential therapeutic target for HCC treatment.
肝细胞癌（HCC）是一种高度恶性的癌症，缺乏有效的治疗靶点。LIM/同源框蛋白Lhx3（LHX3）在各种肿瘤组织中的作用已得到广泛研究，在这些组织中它被确定为肿瘤发生和恶性肿瘤的促进因子。然而，LHX3在人类肝癌中的具体功能作用和潜在机制尚未明确阐明。我们发现，与相邻组织相比，LHX3在肝癌组织中过表达。此外，观察到LHX3促进肝癌细胞的上皮-间质转化（EMT），导致体外增殖、迁移、活力和黏附能力增加。机制上，LHX3促进TCF4与β-连环蛋白结合，形成稳定的LHX3/TCF4/β-连环蛋白复合物，激活下游靶基因。毒黄素破坏β-连环蛋白/TCF4相互作用可阻止肝癌细胞的EMT。总体而言，这些发现突出了LHX3通过β-连环蛋白/TCF4轴在肝癌细胞EMT中的关键作用，表明LHX3/β-连环蛋白/TCF4轴是肝癌治疗的潜在治疗靶点。
