SUMO-specific protease 1 regulates the in vitro and in vivo growth of colon cancer cells with the upregulated expression of CDK inhibitors

Cancer Lett. 2011 Oct 1;309(1):78-84. doi: 10.1016/j.canlet.2011.05.019. Epub 2011 Jun 12.

Abstract

SUMO conjugation emerges as an important mechanism in regulating protein localization, stability and activity. SUMOylation is a dynamic process and can be reversed by a family of sentrin/SUMO-specific proteases (SENPs). However, the biological roles of SENPs in cellular processes are largely unknown. Here, we show that SENP1, a member of SENP family, is overexpressed in most of colon cancer tissues. Silencing of SENP1 expression inhibits cell growth with G(1) arrest in vitro and in nude mice and colony formation in colon cancer cell line DLD-1, suggesting that SENP1 is essential for cell growth in the colon cancer cell line. Accordingly, silencing of SENP1 results in upregulation of CDK inhibitors such as p16, p19, p21 and p27. These results suggest that SENP1 might play a role in cell cycle regulation of colon cancer cells.

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism*
  • Cysteine Endopeptidases
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • G1 Phase / drug effects
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Up-Regulation

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • RNA, Small Interfering
  • Endopeptidases
  • SENP1 protein, human
  • Cysteine Endopeptidases