Research Papers:

Histidine-rich glycoprotein function in hepatocellular carcinoma depends on its N-glycosylation status, and it regulates cell proliferation by inhibiting Erk1/2 phosphorylation

Qinle Zhang _, Kai Jiang, Yan Li, Dongmei Gao, Lu Sun, Shu Zhang, Tianhua Liu, Kun Guo and Yinkun Liu

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Oncotarget. 2015; 6:30222-30231. https://doi.org/10.18632/oncotarget.4997

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Qinle Zhang1,2, Kai Jiang1,2, Yan Li1, Dongmei Gao1, Lu Sun2, Shu Zhang1, Tianhua Liu1,2, Kun Guo1, Yinkun Liu1,2

1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China

2Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China

Correspondence to:

Kun Guo e-mail: [email protected]

Yinkun Liu e-mail: [email protected]

Keywords: hepatocellular carcinoma, histidine-rich glycoprotein, cell proliferation, glycosylation

Received: February 23, 2015     Accepted: July 31, 2015     Published: August 12, 2015


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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