Histidine-rich glycoprotein function in hepatocellular carcinoma depends on its N-glycosylation status, and it regulates cell proliferation by inhibiting Erk1/2 phosphorylation.
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.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
Qinle
Q
Zhang
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
Kai
K
Jiang
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Yan
Y
Li
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Dongmei
D
Gao
Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
Lu
L
Sun
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shu
S
Zhang
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
Tianhua
T
Liu
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Kun
K
Guo
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
Yinkun
Y
Liu
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006031:Glycosylation; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D000099053:Histidine-Rich Glycoprotein
D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
cell proliferation; glycosylation; hepatocellular carcinoma; histidine-rich glycoprotein