Saunders, WS and Wu, Q and Xu, FL and Li, Y and Prochownik, EV
(2010)
The c-Myc target glycoprotein1bα links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells.
PLoS ONE, 5 (5).
Abstract
An increase in chromosome number, or polyploidization, is associated with a variety of biological changes including breeding of cereal crops and flowers, terminal differentiation of specialized cells such as megakaryocytes, cellular stress and oncogenic transformation. Yet it remains unclear how cells tolerate the major changes in gene expression, chromatin organization and chromosome segregation that invariably accompany polyploidization. We show here that cancer cells can initiate increases in chromosome number by inhibiting cell division through activation of glycoprotein1b alpha (GpIbα), a component of the c-Myc signaling pathway. We are able to recapitulate cytokinesis failure in primary cells by overexpression of GpIbα in a p53-deficient background. GpIbα was found to localize to the cleavage furrow by microscopy analysis and, when overexpressed, to interfere with assembly of the cellular cortical contraction apparatus and normal division. These results indicate that cytokinesis failure and tetraploidy in cancer cells are directly linked to cellular hyperproliferation via c-Myc induced overexpression of GpIbα.© 2010 Wu et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Blagosklonny, Mikhail V. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Centers: |
Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute |
Date: |
17 September 2010 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
5 |
Number: |
5 |
DOI or Unique Handle: |
10.1371/journal.pone.0010819 |
Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
Refereed: |
Yes |
MeSH Headings: |
Actins--metabolism; Animals; Cell Transformation, Neoplastic; Cells, Cultured; Contractile Proteins--metabolism; Cytokinesis; Gene Knockdown Techniques; Humans; Membrane Glycoproteins--chemistry; Membrane Glycoproteins--metabolism; Mice; Microfilament Proteins--metabolism; Myosin Heavy Chains--metabolism; Neoplasms--metabolism; Neoplasms--pathology; Phenotype; Protein Sorting Signals; Protein Structure, Tertiary; Protein Transport; Proto-Oncogene Proteins c-myc--metabolism; RNA, Small Interfering--metabolism; Signal Transduction; rhoA GTP-Binding Protein--metabolism |
Other ID: |
NLM PMC2876040 |
PubMed Central ID: |
PMC2876040 |
PubMed ID: |
20520840 |
Date Deposited: |
03 Aug 2012 20:53 |
Last Modified: |
25 Jan 2019 23:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13366 |
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