KCTD10 functions as a tumor suppressor in hepatocellular carcinoma by triggering the Notch signaling pathway

Tao Ma1,2, Daoyuan Wang1,3, Jiajun Wu1,3

  • 1The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Medical College, Hunan Normal University Changsha 410013, Hunan, China.

Abstract

Insights

KCTD10 acts as a tumor suppressor in human hepatocellular carcinoma (HCC). Lowering KCTD10 levels in HCC cells boosts cancer stem cell properties and tumor growth by influencing Notch signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • KCTD10 was previously shown to negatively regulate Notch signaling.
  • The role of KCTD10 in human hepatocellular carcinoma (HCC) carcinogenicity remained unclear.

Purpose of the Study:

  • To investigate the function of KCTD10 in human HCC.
  • To determine if KCTD10 acts as a tumor suppressor in HCC by modulating Notch signaling.

Main Methods:

  • Lentivirus infection was used to manipulate KCTD10 expression in HCC cell lines (Hep3B and MHCC97H).
  • Assessed were tumor sphere formation, cell migration, in vitro and in vivo tumorigenicity, cancer stem cell (CSC) biomarkers (including CD133), and Notch signaling pathway activity.
  • Investigated the impact of KCTD10 knockdown on the Notch1 transmembrane/intracellular region (NTM) and the P53/Notch balance.

Main Results:

  • Down-regulation of KCTD10 significantly enhanced CSC marker gene expression, promoted self-renewal, and increased tumorigenic potential in HCC cells.
  • KCTD10 knockdown led to an increased CD133+ cell population.
  • Reduced KCTD10 expression decreased the NTM of Notch1 and altered the balance between P53 and Notch activity.

Conclusions:

  • KCTD10 functions as a tumor suppressor in HCC.
  • The tumor-suppressive role of KCTD10 in HCC is mediated through its regulation of Notch signaling.

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