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<p>Liver cancer is a leading cause of cancer-related death worldwide. Centrosomal proteins play critical roles in maintaining mitotic fidelity, and their dysregulation contributes to tumorigenesis. Trichoplein (TCHP), a centrosomal protein has recently been implicated in cell cycle progression, but its role in liver cancer remains unclear. In this study, we demonstrate that <i>TCHP</i> is markedly upregulated in hepatocellular carcinoma and hepatoblastoma and is associated with poor patient survival. Functional analyses revealed that <i>TCHP</i> overexpression accelerates hepatocarcinogenesis in mice, while its depletion suppresses tumor growth by inducing mitotic defects and extensive tumor cell death. Mechanistically, TCHP safeguards mitotic fidelity by localizing to centrosomes and promoting liquid–liquid phase separation–driven condensate formation with AURKA, thereby enhancing its activation. Importantly, TCHP inhibition not only suppresses tumor growth directly but also sensitizes liver cancer cells to the AURKA inhibitor alisertib, allowing tumor suppression at reduced drug doses and mitigating toxicity risks. Collectively, our findings establish <i>TCHP</i> as a potential oncogenic driver and therapeutic vulnerability in liver cancer and highlight the TCHP–AURKA axis as a promising target for synergistic treatment strategies.</p>

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TCHP drives hepatocarcinogenesis through LLPS-mediated AURKA condensation and enables synergistic therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月25日

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  • Jingshi Li,
  • Yan Li,
  • Xilang Pan,
  • Shu Wang,
  • Zaisheng Lin,
  • Ruida He,
  • Suning Wang,
  • Xin Huang,
  • Jia-Qi Li,
  • Zhiwei Zhang,
  • Liang Wang,
  • Xiujuan Zhang,
  • Xuxu Sun,
  • Muqing Cao

摘要

Liver cancer is a leading cause of cancer-related death worldwide. Centrosomal proteins play critical roles in maintaining mitotic fidelity, and their dysregulation contributes to tumorigenesis. Trichoplein (TCHP), a centrosomal protein has recently been implicated in cell cycle progression, but its role in liver cancer remains unclear. In this study, we demonstrate that TCHP is markedly upregulated in hepatocellular carcinoma and hepatoblastoma and is associated with poor patient survival. Functional analyses revealed that TCHP overexpression accelerates hepatocarcinogenesis in mice, while its depletion suppresses tumor growth by inducing mitotic defects and extensive tumor cell death. Mechanistically, TCHP safeguards mitotic fidelity by localizing to centrosomes and promoting liquid–liquid phase separation–driven condensate formation with AURKA, thereby enhancing its activation. Importantly, TCHP inhibition not only suppresses tumor growth directly but also sensitizes liver cancer cells to the AURKA inhibitor alisertib, allowing tumor suppression at reduced drug doses and mitigating toxicity risks. Collectively, our findings establish TCHP as a potential oncogenic driver and therapeutic vulnerability in liver cancer and highlight the TCHP–AURKA axis as a promising target for synergistic treatment strategies.