title: Sgo1 is a potential therapeutic target for hepatocellular carcinoma.
abstract: 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.
authors: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Lyu-Han
authors: LH
authors: Wang
authors: Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Chia-Jui
authors: CJ
authors: Yen
authors: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Tian-Neng
authors: TN
authors: Li
authors: Université Laval, Faculty of Medicine, Department of Pediatrics, and Reproduction, Perinatal Health, and Infant Health, Québec, Canada.
authors: Sabine
authors: S
authors: Elowe
authors: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Wen-Ching
authors: WC
authors: Wang
authors: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.|Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan.
authors: Lily Hui-Ching
authors: LH
authors: Wang
mesh_terms: D017398:Alternative Splicing; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008938:Mitosis / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D020033:Protein Isoforms; C496644:SGO1 protein, human
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