title: Proteomics characterization of gastrokine 1-induced growth inhibition of gastric cancer cells.
abstract: We previously used proteomics technology to globally identify gastric cancer-associated proteins and found that gastrokine 1 (GKN1) was dramatically underexpressed in gastric cancer tissues. Here, we further showed that GKN1 could inhibit cell growth and induce cell cycle arrest in gastric cancer cells. The activity of protein kinase PKCδ/θ was inhibited by GKN1, whereas the activity of ERK1/2 and JNK1/2 was increased by GKN1, suggesting that GKN1 induced growth inhibition of gastric cancer cells by synergistically regulating the activity of these protein kinases. Seventy-four proteins were found to be regulated by GKN1 by proteomics analysis, including α-enolase (ENO1) and Cathepsin D. Interestingly, ENO1 is an important hub in the protein-protein interaction network of the 74 differential proteins. Silencing of ENO1 resulted in growth inhibition and cell cycle arrest of gastric cancer cells, similar to the effect of GKN1 overexpression in cells, whereas ENO1 overexpression blocked GKN1-induced growth inhibition and cell cycle arrest. These observations suggested that ENO1 downregulation played an important role in GKN1-induced growth inhibition of gastric cancer cells.
authors.affiliation: Institute of Life and Health Engineering and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, P. R. China.
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Yan
authors.forename: Song-Hui
authors.initials: SH
authors.lastname: Xu
authors.forename: Zi-Lu
authors.initials: ZL
authors.lastname: Tan
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Yin
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D030562:Databases, Protein; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C477000:GKN1 protein, human; D036361:Peptide Hormones; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D020928:Mitogen-Activated Protein Kinases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase