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Knockdown of Golgi phosphoprotein 73 blocks the trafficking of matrix metalloproteinase‐2 in hepatocellular carcinoma cells and inhibits cell invasion
- 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.
- Subjects :
- Male
0301 basic medicine
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
MMP2
intrahepatic metastasis
negative feedback loop
03 medical and health sciences
symbols.namesake
Transactivation
0302 clinical medicine
Downregulation and upregulation
Cell Line, Tumor
Humans
Neoplasm Invasiveness
Secretion
Phosphorylation
Feedback, Physiological
Gene knockdown
Chemistry
Liver Neoplasms
Membrane Proteins
Original Articles
hepatocellular carcinoma
Cell Biology
Golgi apparatus
Cell biology
Gene Expression Regulation, Neoplastic
Protein Transport
030104 developmental biology
Secretory protein
030220 oncology & carcinogenesis
Phosphoprotein
symbols
Matrix Metalloproteinase 2
Molecular Medicine
Original Article
Female
MMP‐2
protein trafficking
GP73
E2F1 Transcription Factor
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....b5a145a1ef2becbe7a27bedd64bb8f0b