Premium
Cyr61 increases matrix metalloproteinase‐3 expression and cell motility in human oral squamous cell carcinoma cells
Author(s) -
Chuang JingYuan,
Yu NuoYi,
Chiang IPing,
Lai ChihHo,
Lin ChiaDer,
Tang ChihHsin
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24066
Subject(s) - cyr61 , focal adhesion , cell migration , cancer research , mapk/erk pathway , mek inhibitor , signal transduction , protein kinase a , extracellular matrix , microbiology and biotechnology , chemistry , kinase , integrin , cell growth , cell , biology , receptor , ctgf , growth factor , biochemistry
Oral squamous cell carcinoma (OSCC) has a striking tendency to migrate and metastasize. 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 effects of Cyr61 on human OSCC cells are largely unknown. In this study, we found that Cyr61 increased the migration and the expression of matrix metalloproteinases‐3 (MMP)‐3 in human OSCC cells. αvβ5 or α6β1 monoclonal antibody (mAb), focal adhesion kinase (FAK) inhibitor, and mitogen‐activated protein kinase (MEK) inhibitors (PD98059 and U0126) inhibited the Cyr61‐induced increase of the migration and MMP‐3 up‐regulation of OSCC cells. Cyr61 stimulation increased the phosphorylation of FAK, MEK, and extracellular signal‐regulated kinase (ERK). In addition, NF‐κB inhibitors suppressed the cell migration and MMP‐3 expression enhanced by Cyr61. Moreover, Cyr61 increased NF‐κB luciferase activity and binding of p65 to the NF‐κB element on the MMP‐3 promoter. Taken together, our results indicate that Cyr61 enhances the migration of OSCC cells by increasing MMP‐3 expression through the αvβ3 or α6β1 integrin receptor, FAK, MEK, ERK, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 1977–1986, 2012. © 2012 Wiley Periodicals, Inc.