Golgi phosphoprotein 73 (GP73) has been regarded as a novel serum biomarker for the diagnosis of hepatocellular carcinoma (HCC) in recent years. It has been reported that the upregulation of GP73 may promote the carcinogenesis and metastasis of HCC; however, the mechanisms remain poorly understood. In this study, GP73 correlates positively with matrix metalloproteinase-2 (MMP-2) in HCC-related cells and tissues. Further studies indicate that the knockdown of GP73 blocks MMP-2 trafficking and secretion, resulting in cell invasion inhibition. Additionally, the knockdown of GP73 induces the accumulation of intracellular MMP-2, which inhibits the phosphorylation of Src at Y416 and triggers the inhibition of SAPK/JNK and p53-p21 signalling pathways through a negative feedback loop. Finally, the transactivation of MMP2 was inhibited by the reduction in E2F1. This study reveals that GP73 plays functional roles in the trafficking and equilibrium of epithelial-mesenchymal transition (EMT)-related secretory proteins and that GP73 serves as a new potential target for combating the metastasis of HCC.
Keywords: GP73; MMP-2; hepatocellular carcinoma; intrahepatic metastasis; negative feedback loop; protein trafficking.
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.