Cyr61 increases migration and MMP-13 expression via alphavbeta3 integrin, FAK, ERK and AP-1-dependent pathway in human chondrosarcoma cells.
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, alphavbeta3 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 alphavbeta3 integrin receptor, FAK, ERK, c-Fos/c-Jun and AP-1 signal transduction pathway.
Tan
Tzu-Wei
TW
Department of Pharmacology, College of Medicine, China Medical University, Taichung, Taiwan.
Yang
Wei-Hung
WH
Lin
Yuh-Tzy
YT
Hsu
Sheng-Feng
SF
Li
Te-Mao
TM
Kao
Shung-Te
ST
Chen
Wen-Chi
WC
Fong
Yi-Chin
YC
Tang
Chih-Hsin
CH
D001859:Bone Neoplasms; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002813:Chondrosarcoma; D055515:Cysteine-Rich Protein 61 / Q000494:pharmacology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D002070:Butadienes; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D005419:Flavonoids; D039302:Integrin alphaVbeta3; D009570:Nitriles; D009842:Oligopeptides; D018808:Transcription Factor AP-1; C113580:U 0126; C047981:arginyl-glycyl-aspartic acid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one