CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway.

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Citation

Tzeng HE, Chen JC, Tsai CH, Kuo CC, Hsu HC, Hwang WL, Fong YC, Tang CH

CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway.

J Cell Physiol. 2011 Dec;226(12):3181-9. doi: 10.1002/jcp.22672.

PubMed ID
21344378 [ View in PubMed
]
Abstract

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene (NOV), regulates proliferation and differentiation of cancer cells. However, the effect of CCN3 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). alphavbeta3 or alphavbeta5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase (PI3K) inhibitors (Ly294002 and wortmannin) and Akt inhibitor inhibited the CCN3-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. CCN3 stimulation increased the phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. In addition, NF-kappaB inhibitors also suppressed the cell migration and MMP-13 expression enhanced by CCN3. Moreover, CCN3 increased NF-kappaB luciferase activity and binding of p65 to the NF-kappaB element on the MMP-13 promoter. Taken together, our results indicate that CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the alphavbeta3/alphavbeta5 integrin receptor, FAK, PI3K, Akt, p65, and NF-kappaB signal transduction pathway.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Protein NOV homologP48745Details