Cyr61 Increases Cell Migration and MMP-3 expression via avb3 and a6b1 Integrins, FAK, ERK and NF-kB Pathways in Human Oral Cancer Cells

• Main Authors: Nuo-Yi Yu, 余諾荑
• Other Authors: Jing-Yuan Chuang
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/55372485481760535247

碩士 === 中國醫藥大學 === 醫學檢驗生物技術學系碩士班 === 99 === Cysteine-rich 61 (Cyr61), one of the CCN gene family members, is a secreted and matrix-associated protein, which is involved in many cellular activities such as growth and differentiation. Most of CCN family members can regulate the cell motility, division and adhesion in various cancer by interaction with integrin. However, the effect of Cyr61 on human oral squamous carcinoma cells is mostly unknown. Here, we found that Cyr61 increased the migration activity and expression of matrix metalloproteinase (MMP)-3 in human oral squamous carcinoma cells (SCC-4 cells). avb3 and a6b1 Integrin monoclonal antibody, focal adhesion kinase (FAK) inhibitor, mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126), and necrosis factor-kappa B (NF-kB) inhibitors (PDTC and TPCK) inhibited the Cyr61-induced increase of the migration and MMP-3 upregulation of human oral squamous carcinoma cells. Cyr61 stimulation increased the phosphorylation of FAK and extracellular signal-regulated kinase (ERK). Moreover, Cyr61 increased the binding of p65 to the NF-kB element on the MMP-3 promoter. Taken together, our results indicated that Cyr61 enhances the migration of human oral squamous carcinoma cells by increasing MMP-3 expression through the avb3 and a6b1 integrin receptor, FAK, ERK, p65 and NF-kB signal transduction pathway.