title: Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis.
abstract: Systematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Yu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D006360:Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D020543:Proteome; C051610:hepatoma-derived growth factor