ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- The AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.The Journal of cell biology · 2026Article
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Lamin B1-dependent regulation of human separase in mitosis.Nucleic acids research · 2026Article
- Separase Inhibition Enhances Gefitinib Sensitivity of Lung Cancer via PTBP1/TAK1/RIPK1-Mediated PANoptosis.MedComm · 2025Article
- Securin regulates the spatiotemporal dynamics of separase.The Journal of cell biology · 2025Article
- Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024Review
- Securin Regulates the Spatiotemporal Dynamics of Separase.bioRxiv : the preprint server for biology · 2023Article
- Gene Expression Pattern ofCancers · 2023Article
- Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer.Frontiers in immunology · 2023Article
- Article
- Mapping separase-mediated cleavage in situ.NAR genomics and bioinformatics · 2022Article
- Reduced sister chromatid cohesion acts as a tumor penetrance modifier.PLoS genetics · 2022Article
- Meiotic behavior, transmission and active genes of B chromosomes in the cichlid Astatotilapia latifasciata: new clues about nature, evolution and maintenance of accessory elements.Molecular genetics and genomics : MGG · 2022Article
- Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase.Cell reports · 2022Article
- Functional analysis of LAT3 in prostate cancer: Its downstream target and relationship with androgen receptor.Cancer science · 2021Article
- Structure and Function of the Separase-Securin Complex.Sub-cellular biochemistry · 2021Review
- ESPL1 Is a Novel Prognostic Biomarker Associated With the Malignant Features of Glioma.Frontiers in genetics · 2021Article
- In silico pathway analysis based on chromosomal instability in breast cancer patients.BMC medical genomics · 2020Article
- A prognostic model based on cell-cycle control predicts outcome of breast cancer patients.BMC cancer · 2020Article
- Centrosome reduction in newly-generated tetraploid cancer cells obtained by separase depletion.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
purposeSeparase, 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
designTo 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.
resultsWe 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.
conclusionThese 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.
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Registered trials
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