title: Nephroblastoma overexpressed gene (NOV) enhances cell motility and COX-2 upregulation of human osteosarcoma involves αvβ5 integrin, ILK and AP-1-dependent pathways.
abstract: Osteosarcoma is characterized by a high malignant and metastatic potential. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin synthase, has been implicated in tumor metastasis. Nephroblastoma overexpressed gene (NOV), also called CCN3, was regulated proliferation and differentiation of cancer cells. However, the effect of NOV on migration activity and COX-2 expression in human osteosarcoma cells is mostly unknown. Here we found that NOV increased the migration and expression of COX-2 in human osteosarcoma cells. αvβ5 monoclonal antibody (mAb), integrin-linked kinase (ILK) and Akt inhibitor reduced the NOV-enhanced the migration and COX-2 up-regulation of osteosarcoma cells. NOV stimulation increased the ILK kinase activity and phosphorylation of Akt. In addition, c-Jun siRNA also antagonized the NOV-mediated migration and COX-2 expression. Moreover, NOV enhanced the AP-1 binding activity and promoter activity. Taken together, these results suggest that the NOV acts through αvβ5 integrin to activate ILK and Akt, which in turn activates c-Jun and AP-1, resulting in the activations of COX-2 and contributing the migration of human osteosarcoma cells.
authors.affiliation: Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan.
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lee
authors.forename: Meng-Yi
authors.initials: MY
authors.lastname: Chen
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Tsai
authors.forename: Horng-Chaung
authors.initials: HC
authors.lastname: Hsu
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D001859:Bone Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D006801:Humans; D055514:Nephroblastoma Overexpressed Protein / Q000502:physiology*; D012516:Osteosarcoma; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
chemical_list: D051546:Cyclooxygenase 2; D055514:Nephroblastoma Overexpressed Protein; D017346:Protein Serine-Threonine Kinases; D019030:Receptors, Vitronectin; D018808:Transcription Factor AP-1; D000099200:Scaffold Protein ILK; C526319:CCN3 protein, human; C064660:integrin alphaVbeta5; C496540:PTGS2 protein, human