Overexpression and constitutive nuclear localization of cohesin protease Separase protein correlates with high incidence of relapse and reduced overall survival in glioblastoma multiforme

Malini Mukherjee, Tiara Byrd, Vita S. Brawley, Kevin Bielamowicz, Xiao Nan Li, Fatima Merchant, Saurabh Maitra, Pavel Sumazin, Greg Fuller, Yvonne Kew, David Sun, Suzanne Zein-Eldin Powell, Nabil M. Ahmed, Nenggang Zhang, Debananda Pati

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Separase, an enzyme that cleaves the chromosomal cohesin during mitosis, is overexpressed in a wide range of human epithelial cancers of breast, bone and prostate (Meyer et al., Clin Cancer Res 15(8):2703-2710, 2009). Overexpression of Separase in animal models results in aneuploidy and tumorigenesis. We have examined the expression and localization of Separase protein in adult and pediatric glioblastoma and normal brain specimens. Immunofluorescence microscopy and Western blot analysis showed significant overexpression of Separase in all adult and a subset of pediatric glioblastoma cells. Tumor status and patient survival strongly correlate with the mislocalization of Separase into the nucleus throughout all stages of the cell cycle. Unlike exclusively nuclear localization in mitotic control cells, glioblastoma samples have a significantly higher number of resting (interphase) cells with strong nuclear Separase staining. Additionally, patient survival analysis demonstrated a strong correlation between overexpression of Separase protein in adult glioblastoma and a high incidence of relapse and reduced overall survival. These results further strengthen our hypothesis that Separase is an oncogene whose overexpression induces tumorigenesis, and indicate that Separase overexpression and aberrant nuclear localization are common in many tumor types and may predict outcome in some human malignancies.

Original languageEnglish (US)
Pages (from-to)27-35
Number of pages9
JournalJournal of Neuro-Oncology
Volume119
Issue number1
DOIs
StatePublished - Aug 2014

Keywords

  • Espl1
  • GBM
  • Separase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

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