Nephroblastoma overexpressed gene (NOV) enhances cell motility and COX-2 upregulation of human osteosarcoma involves alpha v beta 5 integrin, ILK and AP-1-dependent pathways

作者：Huang Chun Yin; Lee Chun Yi; Chen Meng Yi; Tsai Hsiao Chi; Hsu Horng Chaung; Tang Chih Hsin^*

来源：Biochemical Pharmacology, 2011, 81(5): 577-585.

DOI：10.1016/j.bcp.2010.12.005

• NOV
• Integrin
• Osteosarcoma
• Migration
• ILK

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. alpha v beta 5 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 alpha v beta 5 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.

• 出版日期2011-3-1
• 单位中国医科大学