Interaction of Pdcd4 with eIF4E inhibits the metastatic potential of hepatocellular carcinoma.
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.
Jiang
Ying
Y
Department of Gastroenterology, Provincial Hospital, Shandong University, 324, JingWu Road, Jinan Shandong, 250021, PR China.
Zhang
Shu Hong
SH
Han
Guo Qing
GQ
Qin
Cheng Yong
CY
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*
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