Sgo1 is a potential therapeutic target for hepatocellular carcinoma
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Lyu-Han Wang1, Chia-Jui Yen3, Tian-Neng Li1, Sabine Elowe2, Wen-Ching Wang1, Lily Hui-Ching Wang1,4
1Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
2Université Laval, Faculty of Medicine, Department of Pediatrics, and Reproduction, Perinatal Health, and Infant Health, Québec, Canada
3Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan
4Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan
Lily Hui-Ching Wang, e-mail: email@example.com
Keywords: Shugoshin, Hepatocellular Carcinoma, Hepatitis B Virus, Large Surface Antigen, Mitosis, Catastrophe, Cohesin
Received: July 20, 2014 Accepted: November 17, 2014 Published: February 04, 2015
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.
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