title: Recombinant viral capsid protein VP1 suppresses lung cancer metastasis by inhibiting COX-2/PGE2 and MIG-7.
abstract: Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus binds to integrins to modulate Akt/GSK3-β signaling and suppress migration/invasion and metastasis of cancer cells, but the underlying molecular mechanism is unclear. Here, we showed that the rVP1-mediated inhibition of Akt/GSK3-β signaling and cell migration/invasion was accompanied by downregulation in phosphatidylinositol (3,4,5)-triphosphate (PIP3), integrin-linked kinase (ILK) and IKK/NF-κB signaling as well as suppression of COX-2/PGE2 and MIG-7. Addition of PIP3 or overexpression of ILK reversed the rVP1-induced inhibition of IKK/NF-κB signaling, COX-2 and MIG-7. The rVP1-mediated downregulation of COX-2/PGE2 and MIG-7 led to not only attenuation of epithelial-mesenchymal transition, MMP2 activity and invasion of lung cancer cells in vitro but also decreased tumor growth and metastasis of lung cancer in xenograft mice. Moreover, downregulation of COX-2/PGE2 and MIG-7 significantly prolonged the overall and disease-free survival of lung cancer-bearing mice. These results suggest that rVP1 inhibits cancer invasion/metastasis, partly if not mainly, via downregulating integrin/PI3K/Akt, ILK and IKK/NF-κB signaling to suppress expression of COX-2/PGE2 and MIG-7.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Ho
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Hung
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC;Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
chemical_list: D036022:Capsid Proteins; D052246:Cyclooxygenase 2 Inhibitors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C482285:TOX4 protein, human; C442501:VP1 protein, Foot-and-mouth disease virus; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone