In hepatocellular carcinoma (HCC) cells, ECM stiffness up-regulates VEGF expression via the integrin β1/PI3K/Akt pathway and VEGFR2 expression in ECs through the integrin αvβ5/Akt/Sp1 pathway, thus promoting angiogenesis in tumors 30, 31. Here, SP1 is linked to hepatocellular carcinoma.