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Spindle pole body component 25 regulates stemness of prostate cancer cells

机译:主轴极体成分25调节前列腺癌细胞的干性

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摘要

Spindle pole body component 25 (SPC25) is a component of NDC80 complex that controls spindle assembly checkpoint in the microtubule-binding domain of kinetochores. We recently showed that SPC25 is required for prostate cancer (PrC) cell proliferation and cell cycle progression, and here we investigated whether SPC25 may be a Cancer stem cell (CSC) marker in PrC. We found that the levels of SPC25 were higher in PrC samples than paired normal prostate tissue. The overall survival of PrC patients with high SPC25 was poorer than those with low SPC25. PrC cell lines were transduced with two vectors carrying a luciferase reporter and a mCherry fluorescent reporter under a cytomegalovirus promoter and a nuclear green fluorescent protein reporter under the control of a SPC25 promoter, respectively, to allow differentiating SPC25+ from SPC25- PrC cells by flow cytometry. Compared to SPC25- cells, SPC25+ cells formed significantly more tumor spheres in culture, appeared to be more resistant towards docetaxel-induced cell apoptosis, and generated larger tumors with higher frequency after serial adoptive transplantation. Thus, our data suggest that SPC25 may be highly expressed in the CSC-like cells in PrC and could be a promising target for effective treatment of PrC.
机译:主轴极体组件25(SPC25)是NDC80复合体的一个组件,该组件控制动臂微管绑定域中的主轴组件检查点。我们最近表明,前列腺癌(PrC)细胞增殖和细胞周期进程需要SPC25,在这里我们研究了SPC25是否可能是PrC中的癌症干细胞(CSC)标记。我们发现PrC样品中SPC25的水平高于配对的正常前列腺组织。高SPC25的PrC患者的总生存率比低SPC25的患者差。用分别在巨细胞病毒启动子和SPC25启动子控制下携带荧光素酶报告基因和mCherry荧光报告基因的两个载体转导PrC细胞系,以通过流式细胞术区分SPC25 +与SPC25- PrC细胞。与SPC25-细胞相比,SPC25 +细胞在培养中形成明显更多的肿瘤球,似乎对多西他赛诱导的细胞凋亡更有抵抗力,并且在连续过继移植后以更高的频率产生更大的肿瘤。因此,我们的数据表明,SPC25可能在PrC中的CSC样细胞中高表达,并且可能成为有效治疗PrC的有希望的靶标。

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