Wang Lyu-Han, Yen Chia-Jui, Li Tian-Neng, Elowe Sabine, Wang Wen-Ching, Wang Lily Hui-Ching
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Oncotarget. 2015 Feb 10;6(4):2023-33. doi: 10.18632/oncotarget.2764.
Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.
类守护蛋白1（Sgo1）是有丝分裂中的一种必需蛋白；它保护姐妹染色单体黏连，从而确保染色体分离的准确性。我们发现，Sgo1 mRNA在正常组织中的表达相对较低，但在82%的肝细胞癌（HCC）中上调，且与甲胎蛋白升高及HCC的疾病早期发作相关。Sgo1的缺失降低了包括HuH7、HepG2、Hep3B和HepaRG在内的肝癌细胞系的细胞活力。使用延时显微镜，我们发现肝癌细胞在没有Sgo1的情况下有丝分裂延迟并最终死亡。相比之下，永生化细胞的细胞活力和有丝分裂进程未受到显著影响。值得注意的是，当细胞周期蛋白依赖性激酶-1和极光激酶-B受到抑制，或有丝分裂阻滞缺陷蛋白-2缺失时，Sgo1缺失诱导的有丝分裂细胞死亡受到抑制。因此，肝癌细胞中Sgo1缺失诱导的有丝分裂细胞死亡是由纺锤体组装检验点的持续激活介导的。总之，这些结果突出了Sgo1在维持肝癌细胞正常有丝分裂进程中的重要作用，并表明Sgo1是一个有前景的HCC肿瘤靶点。
