CCN3 increases cell motility and ICAM-1 expression in prostate cancer cells
CCN3 increases cell motility and ICAM-1 expression in prostate cancer cells
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DOI：
10.1093/carcin/bgs108
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发表时间：
2012-04-01
期刊：
影响因子：
4.7
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
--
作者：
Chen, Po-Chun;Lin, Tien-Huang;Tang, Chih-Hsin
过表达的肾母细胞瘤（NOV或CCN 3）是一种分泌型基质相关蛋白，属于CCN基因家族，参与许多细胞功能，包括生长、分化和粘附。然而，CCN 3对人类前列腺癌细胞的影响尚不清楚。在这里，我们已经表明，CCN 3增加前列腺癌细胞中的细胞迁移和细胞间粘附分子-1（ICAM-1）的表达。此外，在人前列腺癌细胞中，CCN 3的表达与细胞迁移和ICAM-1的表达呈正相关。CCN 3激活包括α v β 3整联蛋白、整联蛋白连接激酶（ILK）、Akt和核因子-κ B（NF-κ B）的信号转导途径。抑制该途径的特定组分的试剂各自降低CCN 3影响细胞迁移和ICAM-1表达的能力。此外，CCN 3增加了p65与ICAM-1启动子中NF-κ B结合元件的结合。最后，敲低CCN 3表达显著抑制细胞迁移、骨中肿瘤生长和骨转移。综上所述，我们的结果表明，CCN 3通过增加ICAM-1的表达，通过涉及α v β 3整联蛋白，ILK，Akt和NF-κ B的信号转导途径增强前列腺癌细胞的迁移。因此，CCN 3代表了治疗前列腺癌的有希望的新靶点。
Nephroblastoma overexpressed (NOV or CCN3) is a secreted matrix-associated protein that belongs to the CCN gene family and is involved in many cellular functions, including growth, differentiation and adhesion. The effect of CCN3 on human prostate cancer cells, however, is unknown. Here, we have shown that CCN3 increased cell migration and intercellular adhesion molecule-1 (ICAM-1) expression in prostate cancer cells. In addition, expression of CCN3 was positively correlated with both cell migration and ICAM-1 expression in human prostate cancer cells. CCN3 activated a signal transduction pathway that included alpha v beta 3 integrin, integrin-linked kinase (ILK), Akt and nuclear factor-kappaB (NF-kappa B). Reagents that inhibit specific components of this pathway each diminished the ability of CCN3 to effect cell migration and ICAM-1 expression. Moreover, CCN3 increased binding of p65 to an NF-kappa B-binding element in the ICAM-1 promoter. Finally, knockdown of CCN3 expression markedly inhibited cell migration, tumor growth in bone and bone metastasis. Taken together, our results indicate that CCN3 enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves alpha v beta 3 integrin, ILK, Akt and NF-kappa B. CCN3 thus represents a promising new target for treating prostate cancer.