In conclusion, our studies characterized the interaction between S1P and syndecan-1, discovered the S1P1-PI3K/AKT-HPSE -MMP-7 and S1P1/HPSE-ERK1/2 signaling axes that responsible for shedding and inhibition of sydnecan-1, and defined an MMP-7/syndecan-1/TGF-β1 autocrine loop that plays critical roles in HCC metastasis. The gene discussed is MAPK3; the disease is hepatocellular carcinoma.