Other pro-tumorigenic effects of MMP8 may be linked to signaling properties of MMP8: MMP8 itself upregulates TGF-β1 expression by activating the PI3K/Akt/Rac1-pathway, which in turn leads to an epithelial-mesenchymal transition (EMT), and subsequently, increased invasion and migration of hepatocellular carcinoma cells [48]. This evidence concerns the gene MMP8 and hepatocellular carcinoma.