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USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma

Chang Lu1, Zhen Ning1, Aman Wang2

  • 1The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, 116000, China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Cancer Letters
|July 30, 2018
PubMed

Insights

Ubiquitin-specific protease 10 (USP10) acts as a tumor suppressor in hepatocellular carcinoma (HCC) by inhibiting the mTOR pathway. USP10 stabilizes PTEN and AMPKα, thus suppressing tumor growth and improving prognosis in liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulation of the deubiquitination pathway is linked to poor prognosis in cancers like hepatocellular carcinoma (HCC).
  • The mammalian target of rapamycin (mTOR) pathway is a key therapeutic target in HCC, but its regulation by deubiquitination is not fully understood.

Purpose of the Study:

  • To investigate the role of ubiquitin-specific protease 10 (USP10) in regulating the mTOR pathway in HCC.
  • To elucidate the mechanism by which USP10 affects HCC progression and patient prognosis.

Main Methods:

  • Investigated USP10's interaction with PTEN and AMPKα in HCC cells.
  • Assessed the effect of USP10 on PTEN and AMPKα polyubiquitylation and stability.
  • Analyzed AKT phosphorylation and mTOR Complex 1 (mTORC1) activation.
  • Examined USP10 expression levels in human HCC tissues from independent cohorts.

Main Results:

  • USP10 functions as a tumor suppressor in HCC by inhibiting the mTOR pathway.
  • USP10 stabilizes PTEN and AMPKα by preventing their polyubiquitylation.
  • This stabilization leads to inhibition of AKT phosphorylation and mTORC1 activation.
  • USP10 expression is downregulated in HCC tissues, correlating with poor prognosis.

Conclusions:

  • USP10 negatively regulates mTORC1 activation and AKT phosphorylation by stabilizing PTEN and AMPKα in HCC cells.
  • USP10 acts as a tumor suppressor, offering a potential therapeutic target for HCC treatment.
  • This study reveals a novel mechanism linking deubiquitination and mTOR signaling in liver cancer.
Keywords:
DeubiquitinationHCCUSP10mTOR

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