IGFBP2 drives epithelial-mesenchymal transition in Hepatocellular carcinoma via activating the Wnt/β-catenin pathway

Abstract

Abstract Metastasis has emerged as a major impediment to achieving successful therapeutic outcomes in hepatocellular carcinoma (HCC). Nonetheless, the intricate molecular mechanisms governing the progression of HCC remain elusive. Herein, we present evidence highlighting the influence exerted by insulin-like growth factor-binding protein 2 (IGFBP2) as a potent oncogene driving the malignant phenotype. Our investigation reveals a marked elevation of IGFBP2 expression in primary tumors, concomitant with the presence of mesenchymal biomarkers in HCC patients. Through in vitro and in vivo experimentation, we demonstrate that the overexpression of IGFBP2 expedites the progression of epithelial-mesenchymal transition (EMT) and facilitates the metastatic potential of HCC cells, chiefly mediated by the Wnt/β-catenin signaling pathway. Notably, the specific activation of Wnt/β-catenin signaling using CHIR-99021 induces heightened nuclear β-catenin accumulation, thereby instigating a mesenchymal phenotype in HCC cells with depleted IGFBP2 expression. Collectively, our findings identify IGFBP2 as a pivotal regulator within the HCC EMT axis, whereby its overexpression confers the distinctly aggressive clinical features characteristic of the disease.