ITGAV Regulation of LGALS3BP-JUNB Axis Facilitates the Cell-to-Cell Adhesion and Invasiveness of Hepatic Cancer Cells

Background/Aim: ITGAV is a key regulator of hepatocellular carcinoma (HCC) progression, that promotes cell adhesion, migration, and TGF-β1 activation. However, its transcriptional regulation remains poorly understood. This study aimed to elucidate the role of LGALS3BP, a secreted regulator of the TGF-β1 signaling pathway, in ITGAV expression and its functional implications in tumor progression.

Materials and Methods: Public databases (TCGA HCC, GSE271352, GSE271354) and clinical samples from 83 HCC patients at CNUHH were analyzed to investigate the regulation of ITGAV by LGALS3BP and its downstream transcriptional regulator, JUNB. Molecular analyses, including qRT-PCR, western blotting, and ChIP assays, were conducted to assess ITGAV expression and JunB binding at its promoter sites. Functional studies were performed in hepatic cancer cell lines using recombinant LGALS3BP treatment and siRNA-mediated knockdown experiments to evaluate their effects on ITGAV expression and associated phenotypes.

Results: ITGAV expression showed a significant positive correlation with LGALS3BP and JUNB in both TCGA and CNUHH HCC patients. Treatment with recombinant LGALS3BP induced ITGAV expression by enhancing JunB transcriptional activity. Conversely, LGALS3BP knockdown significantly suppressed ITGAV expression, reducing cell-to-cell adhesion and invasiveness in hepatic cancer cells.

Conclusion: The LGALS3BP-JUNB axis regulates ITGAV expression and contributes to HCC progression. Targeting ITGAV, with LGALS3BP as a potential biomarker, and the combined inhibition of both LGALS3BP and ITGAV may represent a promising therapeutic strategy for HCC.