Prospects & Overviews
Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer?
Version of Record online: 18 MAY 2010
Copyright © 2010 WILEY Periodicals, Inc.
Volume 32, Issue 6, pages 468–472, June 2010
How to Cite
Graham, T. A., Jawad, N. and Wright, N. A. (2010), Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer?. Bioessays, 32: 468–472. doi: 10.1002/bies.201000032
- Issue online: 18 MAY 2010
- Version of Record online: 18 MAY 2010
- Cancer Research UK
- The Barts and the London Charity
- asymmetric division;
- cell polarity;
- mitotic spindle alignment;
- stem cells;
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.