A non-genetic route to aneuploidy in human cancers Journal Article

   


Authors: Krajcovic, M.; Johnson, N. B.; Sun, Q.; Normand, G.; Hoover, N.; Yao, E.; Richardson, A. L.; King, R. W.; Cibas, E. S.; Schnitt, S. J.; Brugge, J. S.; Overholtzer, M.
Article Title: A non-genetic route to aneuploidy in human cancers
Abstract: Aneuploidy is common in human tumours and is often indicative of aggressive disease. Aneuploidy can result from cytokinesis failure, which produces binucleate cells that generate aneuploid offspring with subsequent divisions. In cancers, disruption of cytokinesis is known to result from genetic perturbations to mitotic pathways or checkpoints. Here we describe a non-genetic mechanism of cytokinesis failure that occurs as a direct result of cell-in-cell formation by entosis. Live cells internalized by entosis, which can persist through the cell cycle of host cells, disrupt formation of the contractile ring during host cell division. As a result, cytokinesis frequently fails, generating binucleate cells that produce aneuploid cell lineages. In human breast tumours, multinucleation is associated with cell-in-cell structures. These data define a previously unknown mechanism of cytokinesis failure and aneuploid cell formation that operates in human cancers. © 2011 Macmillan Publishers Limited. All rights reserved.
Keywords: controlled study; human tissue; human cell; neoplasms; mitosis; in situ hybridization, fluorescence; cell division; cell structure; models, biological; cell maturation; cell line; cell line, tumor; cell lineage; gene expression regulation, neoplastic; green fluorescent proteins; microscopy, fluorescence; models, genetic; cell nucleus; aneuploidy; intraductal carcinoma; host cell; internalization; cytokinesis; entosis
Journal Title: Nature Cell Biology
Volume: 13
Issue: 3
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2011-03-01
Start Page: 324
End Page: 330
Language: English
DOI: 10.1038/ncb2174
PUBMED: 21336303
PROVIDER: scopus
PMCID: PMC3576821
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-79952264848&partnerID=40&md5=54f6723d0f3d1adb7d9c26f87a3d655d
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 23 June 2011" - "CODEN: NCBIF" - "Source: Scopus"
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MSK Authors
  1. Guillaume Normand
    8 Normand
  2. Michael H Overholtzer
    80 Overholtzer
  3. Qiang Sun
    7 Sun
  4. Matej Krajcovic
    5 Krajcovic
  5. Evelyn Sheau-Yun Yao
    8 Yao
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