Document Detail

Spindles losing their bearings: does disruption of orientation in stem cells predict the onset of cancer?
MedLine Citation:
PMID:  20486132     Owner:  NLM     Status:  MEDLINE    
Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti-tumourigenic mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers.
Trevor A Graham; Noor Jawad; Nicholas A Wright
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  BioEssays : news and reviews in molecular, cellular and developmental biology     Volume:  32     ISSN:  1521-1878     ISO Abbreviation:  Bioessays     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-09-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  8510851     Medline TA:  Bioessays     Country:  United States    
Other Details:
Languages:  eng     Pagination:  468-72     Citation Subset:  IM    
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MeSH Terms
Cell Polarity / physiology
Models, Biological
Neoplasms / metabolism*,  pathology*
Spindle Apparatus / metabolism*
Stem Cells / cytology*,  metabolism,  pathology*
Grant Support
G1000313//Medical Research Council; //Cancer Research UK

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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