Abstract |
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Significantly downregulated histidine-rich glycoprotein ( HRG) during the dynamic stages (WB, WB7, and WB11) of neoplastic transformation of WB F344 hepatic oval-like cells was screened out by iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. HRG expression was significantly lower in HCC tissues. HRG overexpression in Huh7 and MHCC-97H hepatoma cell lines led to decreased cell proliferation, colony-forming ability, and tumor growth, and increased cell apoptosis. HRG could inhibit cell proliferation via the FGF-Erk1/2 signaling pathway by reducing Erk1/2 phosphorylation. On the other hand, the functional expression of HRG was also dependent on the glycosylation status at its N-terminal, especially at the glycosylation site Asn 125. The glycosylation of HRG may play a key competitive role in the interaction between HRG and heparin sulfate for binding bFGF and activating the FGF receptor. These findings provide novel insights into the molecular mechanism of HRG in HCC.
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Authors | Qinle Zhang, Kai Jiang, Yan Li, Dongmei Gao, Lu Sun, Shu Zhang, Tianhua Liu, Kun Guo, Yinkun Liu |
Journal | Oncotarget
(Oncotarget)
Vol. 6
Issue 30
Pg. 30222-31
(Oct 06 2015)
ISSN: 1949-2553 [Electronic] United States |
PMID | 26336134
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proteins
- histidine-rich proteins
- MAPK1 protein, human
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
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Topics |
- Animals
- Apoptosis
- Carcinoma, Hepatocellular
(enzymology, genetics, pathology)
- Cell Line, Tumor
- Cell Proliferation
- Glycosylation
- Humans
- Liver Neoplasms
(enzymology, genetics, pathology)
- Mice, Nude
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Phosphorylation
- Protein Processing, Post-Translational
- Proteins
(genetics, metabolism)
- Proteomics
(methods)
- RNA Interference
- Rats
- Signal Transduction
- Time Factors
- Transfection
- Tumor Burden
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