title: Interaction of Pdcd4 with eIF4E inhibits the metastatic potential of hepatocellular carcinoma.
abstract: Oxidative stress can contribute to the development of hepatocellular carcinoma (HCC) ability of the carcinoma. It has been found that oxidative stress stimulates the phosphorylation of eIF4E primarily through mitogen-activated protein kinase (MAPK) pathways resulting in increased protein translation. Utilizing specific inhibitors of MAPK pathways (SP600125 for c-Jun amino-terminal kinases [JNKs], PD098059 for extracellular signal-regulated kinases [ERKs], and SB203580 for p38 MAPK), we determined that it is primarily the inhibition of JNK that results in the suppression of the increase of p-eIF4E. We also found that PDCD4 inhibits JNK activity resulting in inhibition of the phosphorylation of c-Jun, one isoform of AP-1. We demonstrated that transfection with PDCD4 or inhibition of JNK by SP600125 alters the expression and phosphorylation of eIF4E in the presence of H(2)O(2). PDCD4 results in a stronger inhibitory effect than SP600125.
authors.affiliation: Department of Gastroenterology, Provincial Hospital, Shandong University, 324, JingWu Road, Jinan Shandong, 250021, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Shu Hong
authors.initials: SH
authors.lastname: Zhang
authors.forename: Guo Qing
authors.initials: GQ
authors.lastname: Han
authors.forename: Cheng Yong
authors.initials: CY
authors.lastname: Qin
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000556:secondary*; D045744:Cell Line, Tumor; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008113:Liver Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D018384:Oxidative Stress; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000502:physiology*
chemical_list: D000873:Anthracenes; D051017:Apoptosis Regulatory Proteins; D039561:Eukaryotic Initiation Factor-4E; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C432165:pyrazolanthrone; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9