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| 題名: | CCN3經由FAK, PI3K, AKT 及 NF-κB路徑增加人類軟骨瘤細胞的移行能力
CCN3 increases motility of human chondrosarcoma cell via FAK, PI3K, AKT and NF-κB pathways |
| 作者: | 陳瑞青;Ruei-Ching Chen |
| 貢獻者: | 醫學院基礎醫學研究所 |
| 關鍵詞: | CCN3;細胞黏著受體;人類軟骨瘤細胞;移行金屬蛋白酵素;CCN3;Integrin;Chondrosarcoma cells;Migration;MMP-13. |
| 日期: | 2010 |
| 上傳時間: | 2010-09-29 12:13:45 (UTC+8) |
| 摘要: | NOV是CCN family (Cyr61-CTGF-Nov family) 中的一員，它又可
以稱為CCN3。CCN家族可以進行各種生理的調控如：細胞附著能力、
促進細胞移動及刺激細胞增生作用等...。而CCN3可以透過與細胞表
面的integrin結合進而促進細胞貼附或移動能力，然而CCN3與軟骨肉
瘤的移行並不明朗，在本實驗中我們發現CCN3可以增加人類軟骨肉
瘤細胞的移行和matrix metalloproteinase (MMP)-13的表現。另一方面發現RGD會抑制由CCN3所增加的細胞移行及MMP-13的產生，但給
予RAG peptide時沒有顯著的差異。接著我們使用訊息傳遞抑制劑
FAK mutant、FAK si-RNA、Ly294002、wortmannin、 Akt inhibitor、NF-κB inhibitor (PDTC、TPCK及NF-κB inhibitor peptide)、p85 mutant、Akt mutant、IKKα mutant及IKKβ mutant後，都會抑制CCN3刺激人類軟骨肉瘤細胞的移行能力與MMP-13的產生。給予CCN3後也會促進FAK、PI3K及Akt的活化。這些結果指出CCN3會經過αvβ3及αvβ5 integrin receptor調控人類軟骨肉瘤細胞的移行能力與MMP-13的表現，是透過PI3K/Akt/NF-κB這條路徑。
Nephroblastoma overexpressed (Nov; CCN3), from the CCN gene
family, which is involved in many cellular activities such as growth, differentiation, cell motility, adhesion and division. However, the effect of CCN3 on migration activity in human chandrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 through the αvβ3 and
αvβ5 integrin receptor in human chondrosarcoma cells (JJ012 cells). RGD peptide, αvβ3 and αvβ5 monoclonal antibody but not RAD peptide inhibitor inhibited the CCN3-induced increase migration and MMP-13 expression. Activations of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt and NF-κB pathways after CCN3 treatment was demonstrated, and CCN3-induced expression of MMP-13 and migration activity was inhibited by the specific inhibitor of PI3K, Akt and NF-κB cascades. Transfection of cells with FAK, p85, Akt,
IKKα and IKKβ mutant also reduced CCN3-induced cancer migration. Taken together, our results suggest that CCN3 acts through FAK/PI3K/Akt, which in turn activates NF-κB, resulting in the activation of MMP-13 and contributing to the migration of human chondrosarcoma cells. |
| 顯示於類別: | [基礎醫學研究所] 博碩士論文
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