Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.
Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.
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肝细胞源性生长因子表达下调通过抑制上皮间质转化和MMP2、MMP9来抑制前列腺癌细胞的迁移和侵袭。
DOI：
10.1371/journal.pone.0190725
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Yang F;Yu N;Wang H;Zhang C;Zhang Z;Li Y;Li D;Yan L;Liu H;Xu Z
肝癌衍生生长因子（HDGF）通常过表达，在多种癌症的发生和发展中起着关键作用。先前已经表明，与正常前列腺细胞相比，HDGF在前列腺癌细胞中过度调节，这与前列腺癌的细胞迁移和侵袭相关。在这里，HDGF在前列腺癌中的分子机制进行了研究。显示HDGF敲低降低了前列腺癌细胞在雄激素敏感的LNCaP细胞和雄激素不敏感的DU 145和PC 3细胞中的迁移和侵袭。此外，蛋白质印迹分析显示，HDGF敲低通过上调蛋白E-钙粘蛋白和下调蛋白N-钙粘蛋白、波形蛋白、Snail和Slug来抑制前列腺癌细胞的上皮-间质转化（EMT）。此外，机制研究表明，蛋白质MMP 2和MMP 9被下调。总之，我们的数据表明，HDGF敲低抑制前列腺癌细胞的迁移和侵袭，通过调节上皮间质转化（EMT）信号通路，以及MMP 2和MMP 9信号通路。这些结果支持HDGF是前列腺癌进展中的相关蛋白，并且可能作为前列腺癌及其下游靶标的潜在治疗靶标。
Hepatoma-derived growth factor (HDGF) is commonly over-expressed and plays critical roles in the development and progression in a variety of cancers. It has previously been shown that HDGF is overregulated in prostate cancer cells compared to normal prostate cells, which is correlated with cellular migration and invasion of prostate cancer. Here, the molecular mechanisms of HDGF in prostate cancer is investigated. It is shown that HDGF knockdown reduces prostate cancer cellular migration and invasion in both androgen-sensitive LNCaP cells and androgen-insensitive DU145 and PC3 cells. Furthermore, Western blot analysis reveals that HDGF knockdown inhibits epithelial-mesenchymal transition (EMT) of prostate cancer cells by upregulation of protein E-cadherin and downregulation of proteins N-cadherin, Vimentin, Snail and Slug. In addition, mechanistic studies reveal that proteins MMP2 and MMP9 are down-regulated. In conclusion, our data suggested that HDGF knockdown inhibits cellular migration and invasion in vitro of prostate cancer via modulating epithelial-mesenchymal transition (EMT) signaling pathway, as well as MMP2 and MMP9 signaling pathway. These results supported that HDGF is a relevant protein in the progression of prostate cancer and may serve as a potentially therapeutic target for prostate cancer as well as its downstream targets.
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DOI：
10.1016/j.urolonc.2016.05.027
发表时间：
2016-11-01
影响因子：
2.7
作者：
Shetty, Aditya;Dasari, Subramanyam;Munirathinam, Gnanasekar
通讯作者：
Munirathinam, Gnanasekar
影响因子：
2.5
作者：
Everett, AD
通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
Xu, Ke-sen
影响因子：
4.8
作者：
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通讯作者：
Tai, Ming-Hong