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Dickkopf-1(DKK-1)作为Wnt/β-连环蛋白(Wnt/β-catenin)经典信号传导通路的拮抗剂而受到关注.为了进一步阐明DKK-1在乳腺癌细胞迁移中的作用及其分子机制,应用我们建立的乳腺癌细胞MCF-7高转移倾向亚克隆LM-MCF-7细胞株,比较了DKK-1在不同转移能力的乳腺癌细胞株中表达水平及其与细胞迁移能力的关系.结果显示,DKK-1在LM-MCF-7细胞中表达明显下调;“伤口愈合”实验结果表明,在MCF-7细胞中,RNA干扰DKK-1可导致细胞迁移能力增强;相反,在LM-MCF-7细胞中过表达DKK-1则可抑制细胞的迁移.进一步研究结果显示,DKK-1为肿瘤转移抑制因子nm23的上游激活因子.因此,我们的研究结果表明,DKK-1表达水平下调导致nm23表达水平下调,解除了对乳腺癌细胞迁移的抑制作用,是LM-MCF-7乳腺癌细胞具有高迁移能力的原因之一;反之,与LM-MCF-7相比,DKK-1在MCF-7细胞中高表达,其通过上调nm23可抑制乳腺癌细胞迁移.这一发现对进一步揭示乳腺癌细胞转移的分子机制具有的重要意义.
Dickkopf-1 (DKK-1) is of interest as an antagonist of the classical signaling pathway of Wnt / β-catenin.In order to further elucidate the role of DKK-1 in breast cancer cell migration and its molecular The mechanism of DKK-1 expression in different metastatic breast cancer cell lines and its relationship with cell migration ability was established by subcloning the LM-MCF-7 cell line with MCF-7 highly metastatic breast cancer cell line The results showed that the expression of DKK-1 was significantly down-regulated in LM-MCF-7 cells. The experimental results of “wound healing” showed that RNA interference of DKK-1 in MCF-7 cells resulted in enhanced cell migration ability. DKK-1 overexpression in LM-MCF-7 cells can inhibit cell migration.Further study results show that DKK-1 is an upstream activator of tumor metastasis suppressor nm23 Therefore, our results show that DKK-1 The down-regulation of the expression level of nm23 led to the down-regulation of nm23 expression and the release of the inhibitory effect on breast cancer cell migration, which was one of the reasons for the high migration ability of LM-MCF-7 breast cancer cells. On the contrary, compared with LM-MCF-7, DKK -1 is highly expressed in MCF-7 cells, which can inhibit breast cancer cell migration by up-regulating nm23 This finding is of great significance to further reveal the molecular mechanism of breast cancer cell metastasis.