LHX3 promotes EMT process in hepatoma cell through β-catenin/TCF4 pathway

Abstract Hepatic carcinoma (HCC) is a highly malignant cancer and lacks effective therapeutic targets. The role of 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/β-catenin/TCF4 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.