SKA1 over-expression promotes centriole over-duplication, centrosome amplification and prostate tumourigenesis
SKA1 over-expression promotes centriole over-duplication, centrosome amplification and prostate tumourigenesis
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SKA1 过度表达促进中心粒过度复制、中心体扩增和前列腺肿瘤发生。
DOI：
10.1002/path.4374
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发表时间：
2014-10-01
影响因子：
7.3
通讯作者：
Gao, Wei-Qiang
中科院分区：
文献类型：
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作者：
Li, Jia;Xuan, Jim W.;Gao, Wei-Qiang
虽然纺锤体和着丝点相关蛋白1 （Ska1）先前已被确定为正确染色体分离的必要因素，但尚不清楚它是否在肿瘤发展中起作用。在这里，我们报道Ska1过表达促进前列腺肿瘤的发生。免疫组织化学和定量RT-PCR分析显示，Ska1在人前列腺上皮内瘤变（PIN）和腺癌中过表达，PIN是最可能的前列腺癌前体。Ska1蛋白的上调也被发现在乳腺癌、肺癌和其他常见的人类癌症中具有肿瘤特异性。重要的是，在转基因小鼠模型中，前列腺特异性Ska1上调导致自发肿瘤发生。此外，除了在有丝分裂过程中纺锤体微管和外着丝点界面中丰富外，Ska1在培养细胞的中心体中也丰富。Ska1的缺失导致中心体复制失败，而Ska1的过表达通过诱导中心粒过度复制导致人类前列腺上皮细胞中的中心体扩增。在裸鼠中，这些携带额外中心体的上皮细胞从非致瘤状态转变为致瘤状态。综上所述，这些数据表明Ska1过表达促进了肿瘤的发生。版权所有(c) 2014大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
Although spindle-and kinetochore-associated protein 1 (Ska1) has previously been identified as essential for proper chromosome segregation, it is unknown whether it plays a role in tumour development. Here, we report that Ska1 over-expression promotes prostate tumourigenesis. Immunohistochemistry and quantitative RT-PCR analysis revealed that Ska1 was over-expressed in human prostatic intra-epithelial neoplasia (PIN), the most likely prostate cancer precursor, and adenocarcinomas. Up-regulation of Ska1 protein was also found to be tumour-specific in breast, lung and other common human cancers. Importantly, prostate-specific up-regulation of Ska1 in a transgenic mouse model resulted in spontaneous tumourigenesis. Furthermore, in addition to its abundance in spindle microtubules and the outer kinetochore interface during mitosis, Ska1 was enriched at centrosomes in cultured cells. Depletion of Ska1 caused a failure of centrosome duplication, whilst Ska1 over-expression led to centrosome amplification in human prostate epithelial cells via the induction of centriole over-duplication. These epithelial cells harbouring extra centrosomes switched from a non-tumourigenic to a tumourigenic state in nude mice. Taken together, these data indicate that Ska1 over-expression promotes tumourigenesis. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.