We further used PI3K inhibitor LY294002 to examine the phosphorylation level of Akt and MMP2/MMP9 expressions in HCC cells grown on a high-stiffness substrate; the PI3K inhibitor significantly suppressed the level of Akt phosphorylation and downregulated the expressions of MMP2 and MMP9, indicating that the PI3K/Akt pathway specifically regulates MMP2 and MMP9 expression in HCC cells (Figure 4E). The gene discussed is MMP9; the disease is hepatocellular carcinoma.