Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells
Silencing of the SEC62 gene inhibits migratory and invasive potential of various tumor cells
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DOI：
10.1002/ijc.25580
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发表时间：
2011-05-01
影响因子：
6.4
通讯作者：
Zimmermann, Richard
中科院分区：
文献类型：
--
作者：
Greiner, Markus;Kreutzer, Birgit;Zimmermann, Richard
Sec62是内质网（ER）膜中蛋白质转运装置的一部分。在酵母中，Sec62参与蛋白质翻译后易位到ER中，但其在哺乳动物中的功能仍然难以捉摸。以前，我们描述了SEC62基因在前列腺癌细胞系中的扩增和过表达，并且该蛋白质已被描述为前列腺癌中的潜在靶基因。在目前的研究中，我们表明，在前列腺癌患者的肿瘤组织中，Sec62蛋白水平与来自相同患者或对照组患者的前列腺的无肿瘤组织相比升高，并且更高的Sec62蛋白含量与细胞的去分化增加相关。因此，Sec62蛋白含量的上调确实是与前列腺癌进展相关的现象。多组织肿瘤阵列的分析显示，除了前列腺癌，在各种其他肿瘤中观察到Sec62的过度产生，最显著的是在肺和甲状腺的肿瘤中。为了检查Sec62的肿瘤相关功能，我们用两种不同的SiRNA沉默了前列腺癌细胞系PC 3以及一组其他肿瘤细胞系中的Sec62基因。一般而言，在SEC62沉默后，细胞的细胞迁移和侵袭潜力被阻断或至少显著降低，而细胞活力几乎不受影响。因此，SEC 62基因确实可以被认为是治疗各种肿瘤的靶基因。
Sec62 is part of the protein translocation apparatus in the membrane of the endoplasmic reticulum (ER). In yeast, Sec62 participates in the post-translational translocation of proteins into the ER, but its function in mammals remains elusive. Previously we described the amplification and over-expression of the SEC62 gene in prostate cancer cell lines and the protein has been described as a potential target gene in prostate cancer. In the current study we show that in the tumor tissue of prostate cancer patients Sec62 protein levels are elevated compared with tumor-free tissue derived from the same patients or from prostates of control group patients and that the higher Sec62 protein content correlates with an increasing dedifferentiation of the cells. Therefore, up-regulation of Sec62 protein content indeed is a phenomenon associated with prostate cancer progression. Analysis of a multi-tissue tumor array showed that in addition to prostate cancer, overproduction of Sec62 is observed in various other tumors, most significantly in tumors of the lung and the thyroid. To examine the tumor-related functions of Sec62, we silenced the SEC62 gene in the prostate cancer cell-line PC3 as well as in a set of other tumor cell-lines with two different siRNAs. In general, after silencing of SEC62 the cell migration and the invasive potential of the cells was blocked or at least dramatically reduced while cell viability was hardly affected. Thus, the SEC62 gene may indeed be considered as a target gene in the therapy of various tumors.