In addition, higher matrix stiffness also upregulates osteopontin (OPN) expression in HCC cells by activating integrin β1/GSK3β/β-catenin signaling pathway [17], and forces the expression of vascular endothelial growth factor through integrin β1/AKT/PI3K signaling pathway [14], thereby suggesting that it may participate in the regulation of the expression levels of some invasion/metastasis-associated genes and ultimately influence HCC metastasis. The gene discussed is SPP1; the disease is hepatocellular carcinoma.