Des-γ-carboxyl prothrombin induces matrix metalloproteinase activity in hepatocellular carcinoma cells by involving the ERK1/2 MAPK signalling pathway

Pan, Yue; Gao, Zu–Hua; Xue, Xindong; Cui, Shu‐Xiang; Zhao, Cuirong; Yuan, Yi; Yin, Zhe; Inagaki, Yoshiaki; Kokudo, Norihiro; Tang, Wei; Qu, Xian‐Jun

doi:10.1016/j.ejca.2011.01.017

Cited by 40 publications

(38 citation statements)

References 43 publications

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“…Research has proven that DCP can bind with the surface receptor c-Met and result in c-Met phosphorylation (31). The current authors previously found that DCP can activate c-Met and induce matrix metalloproteinase activity in HCC cells, thus promoting the migration and invasion of HCC cells in vitro (32). The possible interaction between DCP and c-Met in human HCC was evident in the results of the present study, i.e.…”

Section: Influence Of Dcp/c-met Expression On Hcc Recurrencesupporting

confidence: 67%

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

et al. 2012

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Section: Influence Of Dcp/c-met Expression On Hcc Recurrencesupporting

confidence: 67%

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

et al. 2012

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“…In HLE and SK-Hep which are the DCP-negative cell lines, DCP with 10-160 ng/ml for 24 h exposure significantly increased the expression of the phosphorylated c-Met by up to 106.2%. Its downstream signals such as EGFR and MMPs were consequently activated [64]. In response to DCP stimulation, DNA synthesis was activated, and the proliferation and migration of HCC cells were consequently increased.…”

Section: The Stimulator Of Hcc Growth and Invasionmentioning

confidence: 99%

Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

Zhang

Chu

Cui

et al. 2014

Cell Physiol Biochem

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Des-γ-carboxy prothrombin (DCP) is a prothrombin precursor produced in hepatocellular carcinoma (HCC). Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu) residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla) residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs) and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

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“…DCP stimulates HCC growth and promotes HCC metastasis by increasing MMP-2 and MMP-9 activity by activation the ERK1/2 MAPK signaling pathway (Yue et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses

Samanoudy¹,

Monir²,

Badawy³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. In Egypt, the incidence of HCC has doubled over the last decade. Matrix metalloproteinase-9 (MMP-9) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C)/ thymidine (T) single nucleotide polymorphism at position -1562 in the MMP-9 promoter is reported to influence the expression of the MMP-9 gene. The association between MMP-9 gene polymorphisms and HCC patients with hepatitis C and B viruses (HCV and HBV) was examined in 91 patients with HCC and viral hepatitis (55 HCV and 36 HBV). The results were compared with those of 42 HCC patients without viral hepatitis and 60 healthy individuals with no liver infection. Polymorphisms of the MMP-9 gene were investigated by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis. The serum MMP-9 level was quantitatively determined using a human MMP-9 enzyme-linked immunosorbent assay, which showed that homozygosity of the MMP-9 promoter (TT) was more frequent in patients with HCC and chronic HCV or HBV infection when compared with the control group (49.1, 52.8, and 35.7%, respectively). In addition, we observed significant elevation of serum MMP-9 levels in all HCC groups compared to controls. It was concluded that patients with the MMP-9 TT genotype are at risk of developing HCC and HBV or HCV. People with significantly elevated serum levels of MMP-9 are at risk of developing HCC.

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Des-γ-carboxyl prothrombin induces matrix metalloproteinase activity in hepatocellular carcinoma cells by involving the ERK1/2 MAPK signalling pathway

Cited by 40 publications

References 43 publications

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses

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Des-γ-carboxyl prothrombin induces matrix metalloproteinase activity in hepatocellular carcinoma cells by involving the ERK1/2 MAPK signalling pathway

Cited by 40 publications

References 43 publications

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

Des-γ-carboxy prothrombin and c-Met were concurrently and extensively expressed in hepatocellular carcinoma and associated with tumor recurrence

Des-&#947;-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

Matrix metalloproteinase-9 gene polymorphism in hepatocellular carcinoma patients with hepatitis B and C viruses

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Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma