Journal Article

Cyr61 increases migration and MMP-13 expression via αvβ3 integrin, FAK, ERK and AP-1-dependent pathway in human chondrosarcoma cells

Tzu-Wei Tan, Wei-Hung Yang, Yuh-Tzy Lin, Sheng-Feng Hsu, Te-Mao Li, Shung-Te Kao, Wen-Chi Chen, Yi-Chin Fong and Chih-Hsin Tang

in Carcinogenesis

Volume 30, issue 2, pages 258-268
Published in print February 2009 | ISSN: 0143-3334
Published online January 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn284
Cyr61 increases migration and MMP-13 expression via αvβ3 integrin, FAK, ERK and AP-1-dependent pathway in human chondrosarcoma cells

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Cysteine-rich 61 (Cyr61), from the CCN gene family, is a secreted and matrix-associated protein, which is involved in many cellular activities such as growth and differentiation. However, the effect of Cyr61 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that Cyr61 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). RGD peptide, αvβ3 monoclonal antibody and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the Cyr61-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. Cyr61 stimulation increased the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). In addition, activator protein-1 (AP-1) decoy oligodeoxynucleotide also suppressed the MMP-13 messenger RNA and enzyme activity enhanced by Cyr61. Moreover, Cyr61 increased the binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter. Taken together, our results indicated that Cyr61 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the αvβ3 integrin receptor, FAK, ERK, c-Fos/c-Jun and AP-1 signal transduction pathway.

Journal Article.  6427 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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