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骨桥蛋白(osteopontin,OPN)是一种分泌型非胶原性富含硅铝酸的趋化因子样蛋白,属小整合素结合配体N连接糖蛋白(SIBLING)家族成员,在许多肿瘤中具有重要的致癌作用,其配体是整合素和CD44。我们的研究发现,OPN可以通过和CD44的作用上调结肠癌细胞株HT29内果蝇Zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)的表达和其活性,导致组蛋白3第27位赖氨酸三甲基化(H3K27me3)水平增高,对结肠癌细胞具有显著的促增殖作用。通过阻断OPN或利用EZH2特异性抑制剂(GSK126)可以抑制结肠癌细胞的体内外的增殖,从而具有潜在的临床应用价值。
Osteopontin (OPN) is a secreted, non-collagenous aluminosilicate-rich chemokine-like protein that is a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family and has in many tumors Important oncogenic effects of its ligands are integrins and CD44. Our study found that OPN can up-regulate the expression and activity of Zeste homolog 2 (EZH2) in colon cancer cell line HT29 by interacting with CD44. Lysine trimethylation (H3K27me3) increased levels of colon cancer cells had a significant role in promoting proliferation. By blocking OPN or using EZH2 specific inhibitor (GSK126) can inhibit the proliferation of colon cancer cells in vitro and in vivo, which has potential clinical value.