骨桥蛋白促进结肠癌细胞增殖的机制研究

Study on the mechanism by which osteopontin promotes proliferation of colorectal cancer cells

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。

Abstract： Osteopontin （OPN） is a secreted sialic acidrich, non-collagenous chemokine-like protein, it belongs to the family of small integrin-binding ligand N-linked glycoprotein （SIBLING） members and it has important roles in determining the oncogenic potential of various cancers. The ligands of OPN are integrins and CD44. It was found in the present study that, OPN-CD44interaction could significantly promote the proliferation of colorectal cancer cell lines, the mechanism refers not only to an increased expression level of enhancer of zeste homolog 2 （EZH2） but also to an upregulation of EZH2 activity through trimethy lation of histone H3 on lysine 27 （H3K27me3） in the colorectal cell line HT29. Inhibiting OPN could block proliferation of HT29 cells in vitro, while GSK-126, a specific inhibitor of EZH2, could suppress the growth of HT29 cells in vivo. These findings provide potential clinical value in the treatment of colorectal cancers.