RETRACTED: MIG-7 Controls COX-2/PGE2-Mediated Lung Cancer Metastasis (Retracted article. See vol. 79, pg. 4553, 2019)

被引:45
作者
Ho, Ming-Yi [1 ]
Liang, Shu-Mei [1 ,2 ]
Hung, Shao-Wen [2 ]
Liang, Chi-Ming [1 ,2 ,3 ]
机构
[1] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan
[2] Acad Sinica, ABRC, Taipei 11529, Taiwan
[3] Acad Sinica, Inst Biol Chem, Taipei 11529, Taiwan
关键词
CELL-SPECIFIC MIG-7; MATRIX-METALLOPROTEINASE; TUMOR-GROWTH; CARCINOMA; AKT; EXPRESSION; INVASION; COX-2; CYCLOOXYGENASE-2; ACTIVATION;
D O I
10.1158/0008-5472.CAN-12-2220
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
More effective treatments for metastatic lung cancer remain a pressing clinical need. In this study, we identified migration inducting gene-7 (MIG-7) protein as critical for COX-2/prostaglandin E2 (PGE2)- and Akt/GSK-3 beta-dependent tumor invasion/metastasis. COX-2/PGE2 activated EP4 to enhance Akt and GSK-3 beta phosphorylation and beta-catenin/T-cell factor/lymphoid enhancer factor signaling leading to MIG-7 upregulation. RNAi-mediated attenuation of MIG-7 blocked COX-2/PGE2-and Akt/GSK-3 beta-mediated migration/invasion effects. Furthermore, MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK-3 beta phosphorylation and cancer-cell migration/invasion. Cancer cells overexpressing MIG-7 exhibited increased expression of ZEB-1 and Twist in parallel with epithelial-mesenchymal transition, metastasis and cancer lethality. MIG-7 protein level positively correlated with advanced stages of human lung cancers. MIG-7 thus offers a theranostic target for cancer metastases arising from aberrant activation of the cellular COX-2/PGE2 and Akt/GSK-3 beta signaling pathways. Cancer Res; 73(1); 439-49. (C)2012 AACR.
引用
收藏
页码:439 / 449
页数:11
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