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首页> 外文期刊>Cancer science. >Dickkopf‐1 inhibits epithelial‐mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
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Dickkopf‐1 inhibits epithelial‐mesenchymal transition of colon cancer cells and contributes to colon cancer suppression

机译：Dickkopf-1抑制结肠癌细胞的上皮-间质转化并有助于抑制结肠癌

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AbstractThis study aimed to determine the expression pattern of dickkopf-1 (Dkk1), a potent inhibitor of Wnt signaling, in colon cancer and to assess the function and mechanism of Dkk1 in tumor progression in vitro and in vivo. We detected the protein expression of Dkk1 and some epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin, vimentin and β-catenin) in 217 tissue samples of human colon cancer, upregulated Dkk1 expression in HCT116 colon cancer cells, and established a nude mouse xenograft model. Dkk1 protein overexpression was inversely related to tumor grade and the presence of metastasis and recurrence of colon cancer. Notably, the expression of Dkk1 was concomitant with reduced immunohistochemical features of EMT (e.g. increased expression of epithelial marker E-cadherin, decreased expression of mesenchymal marker vimentin, and cytoplasmic distribution of β-catenin). Furthermore, Dkk1 overexpression resulted in restoration of the epithelial phenotype, decreased expression of EMT transcription factors Snail and Twist, and decreased expression of markers suggestive of intestinal stem cells (e.g. cluster of differentiation 133 [CD133] and leucine-rich-repeat-containing G-protein-coupled receptor 5 [Lgr5]). Functional analysis showed overexpression of Dkk1 reduced proliferation, migration, and invasion of colon cancer cells. Moreover, upregulation of Dkk1 led to decreased tumor-initiating ability and suppressed colon tumor growth in nude mice. Our findings indicate that Dkk1 can suppress the progression of colon cancer, possibly through EMT inhibition, and could therefore serve as a target for tumor therapy. (Cancer Sci 2012; 103: 828–835)
机译：摘要本研究旨在确定Wnt信号的有效抑制剂dickkopf-1（Dkk1）在结肠癌中的表达模式，并评估Dkk1在体内外肿瘤发展中的功能和机制。我们在217例人类结肠癌组织样本中检测了Dkk1的蛋白表达和一些上皮-间质转化（EMT）相关标记（E-钙粘蛋白，波形蛋白和β-连环蛋白），并在HCT116结肠癌细胞中上调了Dkk1表达，并建立了裸鼠异种移植模型。 Dkk1蛋白的过表达与肿瘤的分级以及结肠癌的转移和复发呈负相关。值得注意的是，Dkk1的表达与EMT的免疫组织化学特征降低（例如上皮标记E-钙黏着蛋白的表达增加，间质标记波形蛋白的表达减少和β-连环蛋白的细胞质分布）相关。此外，Dkk1的过表达导致上皮表型的恢复，EMT转录因子Snail和Twist的表达降低以及暗示肠道干细胞的标志物的表达降低（例如分化簇133 [CD133]和富含亮氨酸的重复G） -蛋白偶联受体5 [Lgr5]。功能分析表明，Dkk1的过表达减少了结肠癌细胞的增殖，迁移和侵袭。此外，Dkk1的上调导致裸鼠体内的肿瘤启动能力降低并抑制了结肠肿瘤的生长。我们的发现表明，Dkk1可以通过抑制EMT抑制结肠癌的进展，因此可以作为肿瘤治疗的靶标。 （Cancer Sci 2012; 103：828-835）

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