In HCC, the activation and upregulation of Piezo1 inhibit hypoxia-inducible factor 1 (HIF-1) ubiquitination, which in turn enhances the expression and secretion of downstream pro-angiogenic factors such as vascular endothelial growth factor (VEGF), CXC chemokine ligand 16 (CXCL16) and insulin-like growth factor binding protein 2 (IGFBP2), ultimately accelerating HCC angiogenesis (Li M. et al., 2022). Here, IGFBP2 is linked to hepatocellular carcinoma.