title: MIG-7 controls COX-2/PGE2-mediated lung cancer metastasis.
abstract: 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-3β-dependent tumor invasion/metastasis. COX-2/PGE2 activated EP4 to enhance Akt and GSK-3β phosphorylation and β-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-3β-mediated migration/invasion effects. Furthermore, MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK-3β 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-3β signaling pathways.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Ho
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Hung
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
mesh_terms: D000818:Animals; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis
chemical_list: D009363:Neoplasm Proteins; C482285:TOX4 protein, human; D051546:Cyclooxygenase 2; D015232:Dinoprostone