Cyr61  增加口腔癌細胞移行及 MMP-3 表現經由avb3  及
a6b1 Integrins, FAK, ERK 和 NF-kB 路徑

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Title:	Cyr61 增加口腔癌細胞移行及 MMP-3 表現經由avb3 及 a6b1 Integrins, FAK, ERK 和 NF-kB 路徑 Cyr61 Increases Cell Migration and MMP-3 expression via avb3 and a6b1 Integrins, FAK, ERK and NF-kB Pathways in Human Oral Cancer Cells
Authors:	余諾荑
Contributors:	醫學檢驗生物技術學系碩士班
Keywords:	口腔癌;移行;MMP;NF-Kb Oral cancer;Migration;MMP;NF-kB
Date:	2011-08-01
Issue Date:	2011-10-17 16:56:49 (UTC+8)
Publisher:	中國醫藥大學
Abstract:	Cyr61 為 CCN 蛋白家族的成員，為一分泌型蛋白並與細胞外基質結合，主要參與調控細胞的生長及分化作用。絕大多數的 CCN 蛋白成員可調控各種腫瘤細胞的移動性、細胞分裂以及細胞的依附性。然而，Cyr61 對口腔癌的影響目前仍不清楚，此次研究我們主要發現Cyr61 增加口腔癌細胞(SCC-4)的移動性以及 MMP-3 的表現。avb3以及a6b1 Integrin 的抗體、FAK 抑制劑、MEK 抑制劑(PD98059 和 U0126)，以及 NF-kB 抑制劑(PDTC 和 TPCK)皆抑制了 Cyr61 所促進的口腔癌細胞移動能力以及 MMP-3 的表現，Cyr61 的刺激增加了FAK 以及 ERK 的磷酸化，進而促進了 NF-kB 的 p65 次單元結合上MMP-3 啟動子的能力。綜合以上所述，我們的結果顯示 Cyr61 促進口腔癌細胞轉移能力及 MMP-3 表現，且是經由avb3 及a6b1 Integrins, FAK, ERK 和 NF-kB 訊息傳遞路徑。 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.
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