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Updated: Apr 18, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Sgo1 is a potential therapeutic target for hepatocellular carcinoma
Lyu-Han Wang1, Chia-Jui Yen2, Tian-Neng Li1
1Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
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.
Insights
Shugoshin-like protein 1 (Sgo1) is crucial for mitosis in liver cancer cells. Its depletion causes mitotic cell death, suggesting Sgo1 is a potential therapeutic target for hepatocellular carcinoma (HCC).
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Shugoshin-like protein 1 (Sgo1) is vital for maintaining sister chromatid cohesion during mitosis.
- Sgo1 ensures accurate chromosome segregation, a process critical for preventing aneuploidy.
Purpose of the Study:
- To investigate the role of Sgo1 in hepatocellular carcinoma (HCC) pathogenesis.
- To explore Sgo1 as a potential therapeutic target for HCC.
Main Methods:
- Analysis of Sgo1 mRNA expression in normal tissues versus HCC.
- Depletion of Sgo1 in hepatoma cell lines (HuH7, HepG2, Hep3B, HepaRG) and immortalized cells.
- Time-lapse microscopy to observe mitotic progression and cell viability.
- Investigating the effect of inhibiting key mitotic regulators (CDK1, Aurora B) and MAD2 depletion on Sgo1-depleted cells.
Main Results:
- Sgo1 mRNA is upregulated in 82% of HCC cases, correlating with elevated alpha-fetoprotein and earlier disease onset.
- Sgo1 depletion significantly reduces hepatoma cell viability and induces mitotic delay and cell death.
- Mitotic cell death in Sgo1-depleted hepatoma cells is dependent on persistent spindle assembly checkpoint activation.
- Immortalized cells show no significant impact on viability or mitosis upon Sgo1 depletion.
Conclusions:
- Sgo1 plays an essential role in maintaining mitotic progression in hepatoma cells.
- Sgo1 is a promising oncotarget for the development of novel HCC therapies.
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