| Summary: | 碩士 === 中國醫藥大學 === 基礎醫學研究所 === 98 === Nephroblastoma overexpressed (Nov; CCN3), from the CCN gene
family, which is involved in many cellular activities such as growth, differentiation, cell motility, adhesion and division. However, the effect of CCN3 on migration activity in human chandrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 through the αvβ3 and
αvβ5 integrin receptor in human chondrosarcoma cells (JJ012 cells). RGD peptide, αvβ3 and αvβ5 monoclonal antibody but not RAD peptide inhibitor inhibited the CCN3-induced increase migration and MMP-13 expression. Activations of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt and NF-κB pathways after CCN3 treatment was demonstrated, and CCN3-induced expression of MMP-13 and migration activity was inhibited by the specific inhibitor of PI3K, Akt and NF-κB cascades. Transfection of cells with FAK, p85, Akt,
IKKα and IKKβ mutant also reduced CCN3-induced cancer migration. Taken together, our results suggest that CCN3 acts through FAK/PI3K/Akt, which in turn activates NF-κB, resulting in the activation of MMP-13 and contributing to the migration of human chondrosarcoma cells.
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