Taken together, these results demonstrate that MUC1-induced JNK activation not only enhances the phosphorylation of Smad2C through TGF-β/TβRI, but also directly enhances the phosphorylation of Smad2L, and then both of them collaborate to upregulate the MMP-9-mediated cell migration and invasion of HCC cells. The gene discussed is MUC1; the disease is hepatocellular carcinoma.