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Knockdown of Golgi phosphoprotein 73 blocks the trafficking of matrix metalloproteinase‐2 in hepatocellular carcinoma cells and inhibits cell invasion

Authors :
Linfu Zhou
Sining Zhou
Anbang Wei
Jia He
Yiming Liu
Zhi Chen
Yun Xu
Feng Lin
Xiaodi Zhang
Jieyao Shi
Source :
Journal of Cellular and Molecular Medicine
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

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.

Details

ISSN :
15824934 and 15821838
Volume :
23
Database :
OpenAIRE
Journal :
Journal of Cellular and Molecular Medicine
Accession number :
edsair.doi.dedup.....b5a145a1ef2becbe7a27bedd64bb8f0b
Full Text :
https://doi.org/10.1111/jcmm.14055