Roles and Signaling Pathways of Des-γ-Carboxyprothrombin in the Progression of Hepatocellular Carcinoma.
Des-γ-carboxyprothrombin (DCP), an abnormal prothrombin produced in human hepatocellular carcinoma (HCC), plays crucial roles in the progression of HCC. DCP binding to cellular mesenchymal-epithelial transition factor (c-Met) is an initial event and consequently stimulates HCC through the increase of c-Met-Janus kinase 1- signal transducers and activators of transcription pathways. DCP stimulates HCC invasion through activation of matrix metalloproteinase via upregulation of extracellular signal-regulated kinase-mitogen-activated protein kinase (MAPK) pathway. DCP stimulates HCC angiogenesis through activation of the DCP-kinase insert domain receptor-phospholipaseC-γ-MAPK pathway. Identification of these pathways is important for designing the therapeutic strategy for HCC.
a Beijing Key Laboratory of Environmental Toxicology, School of Public Health , Capital Medical University , Beijing , China.
Shu-Xiang
SX
Cui
b Department of Pharmacology , School of Basic Medical Sciences, Capital Medical University , Beijing , China.
Xin-Feng
XF
Yu
b Department of Pharmacology , School of Basic Medical Sciences, Capital Medical University , Beijing , China.
Xian-Jun
XJ
Qu
D015415:Biomarkers / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D051966:Phospholipase C gamma / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism*; D011516:Prothrombin / Q000096:biosynthesis / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D015415:Biomarkers; D011498:Protein Precursors; D050796:STAT3 Transcription Factor; C008208:acarboxyprothrombin; D011516:Prothrombin; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2; D053613:Janus Kinase 1; D020928:Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma
Human hepatocellular carcinoma (HCC); KDR–PLC-γ–MAPK pathway; angiogenesis; angiogenic stimulator; autologous growth factor; c-Met–JAK–STAT3 pathway; des-γ-carboxyprothrombin (DCP)