Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers

Rene Meyer, Viacheslav Fofanov, Anilk Panigrahi, Fatima Merchant, Nenggang Zhang, Debananda Pati

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Purpose: Separase, an endopeptidase, plays a pivotal role in chromosomal segregation by separating sister chromatids during the metaphase to anaphase transition. Using a mouse mammary tumor model we have recently shown that overexpression of Separase induces aneuploidy and tumorigenesis (Zhang et al., Proc Natl Acad Sci 2008;105:13033). In the present study, we have investigated the expression level of Separase across a wide range of human tumors. Experimental Design: To examine the expression levels and localization of Separase in human tumors, we have performed immunofluorescence microscopy using human Separase antibody and tumor tissue arrays from osteosarcoma, colorectal, breast, and prostate cancers with appropriate normal controls. Results: We show that Separase is significantly overexpressed in osteosarcoma, breast, and prostate tumor specimens. There is a strong correlation of tumor status with the localization of Separase into the nucleus throughout all stages of the cell cycle. Unlike the normal control tissues, where Separase localization is exclusively cytoplasmic in nondividing cells, human tumor samples show significantly higher number of resting cells with a strong nuclear Separase staining. Additionally, overexpression of Separase transcript strongly correlates with high incidence of relapse, metastasis, and lower 5-year overall survival rate in breast and prostate cancer patients. Conclusion: These results further strengthen our hypothesis that Separase might be an oncogene, whose overexpression induces tumorigenesis, and indicates that Separase overexpression and aberrant nuclear localization are common in many tumor types and may predict outcome in some human cancers.

Original languageEnglish (US)
Pages (from-to)2703-2710
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number8
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers'. Together they form a unique fingerprint.

Cite this