Open AccessKnockdown of Golgi phosphoprotein 73 blocks the trafficking of matrix metalloproteinase‐2 in hepatocellular carcinoma cells and inhibits cell invasion
Author(s) -
Liu Yiming,
Zhang Xiaodi,
Zhou Sining,
Shi Jieyao,
Xu Yun,
He Jia,
Lin Feng,
Wei Anbang,
Zhou Linfu,
Chen Zhi
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14055
Subject(s) - gene knockdown , cancer research , metastasis , epithelial–mesenchymal transition , matrix metalloproteinase , chemistry , microbiology and biotechnology , downregulation and upregulation , biology , cell culture , cancer , medicine , biochemistry , genetics , gene
Golgi phosphoprotein 73 ( GP 73) 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 GP 73 may promote the carcinogenesis and metastasis of HCC ; however, the mechanisms remain poorly understood. In this study, GP 73 correlates positively with matrix metalloproteinase‐2 ( MMP ‐2) in HCC ‐related cells and tissues. Further studies indicate that the knockdown of GP 73 blocks MMP ‐2 trafficking and secretion, resulting in cell invasion inhibition. Additionally, the knockdown of GP 73 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 MMP 2 was inhibited by the reduction in E2F1. This study reveals that GP 73 plays functional roles in the trafficking and equilibrium of epithelial‐mesenchymal transition ( EMT )‐related secretory proteins and that GP 73 serves as a new potential target for combating the metastasis of HCC .