SENP2 regulates hepatocellular carcinoma cell growth by modulating the stability of β-catenin

Asian Pac J Cancer Prev. 2012;13(8):3583-7. doi: 10.7314/apjcp.2012.13.8.3583.


SUMOylation has emerged as an important post-translational modification that modulates the localization, stability and activity of a broad spectrum of proteins. A dynamic process, it can be reversed by a family of SUMO- specific proteases (SENPs). However, the biological roles of SENPs in mammalian development and pathogenesis remain largely elusive. Here, we demonstrated that SENP2 plays a critical role in the control of hepatocellular carcinoma cell growth. SENP2 was found to be down-regulated in hepatocellular carcinoma (HCC) tissues and over-expression suppressed the growth and colony formation of HCC cells. In contrast, silencing of SENP2 by siRNAs promoted cancer cell growth. We further found that stability of β-catenin was markedly decreased when SENP2 was over-expressed. Interestingly, the decrease was dependent on the de-SUMOylation activity of SENP2, because over-expression of a SENP2 catalytic mutant form had no obviously effects on β-catenin. Our results suggest that SENP2 might play a role in hepatocellular carcinoma cell growth control by modulating the stability of β-catenin.

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation*
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sumoylation
  • Tumor Cells, Cultured
  • beta Catenin / chemistry*
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • RNA, Messenger
  • RNA, Small Interfering
  • beta Catenin
  • Cysteine Endopeptidases
  • SENP2 protein, human