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Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells

Chromosomal instability (CIN) is defined as the perpetual missegregation of whole chromosomes during mitosis and represents a hallmark of human cancer. However, the mechanisms influencing CIN and its consequences on tumour growth are largely unknown. We identified an increase in microtubule plus-end...

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Bibliographic Details
Main Authors: Ertych, Norman (Author) , Stolz, Ailine (Author) , Stenzinger, Albrecht (Author) , Weichert, Wilko (Author) , Kaulfuß, Silke (Author) , Burfeind, Peter (Author) , Aigner, Achim (Author) , Wordeman, Linda (Author) , Bastians, Holger (Author)
Format: Article (Journal)
Language:English
Published: 29 June 2014
In: Nature cell biology
Year: 2014, Volume: 16, Issue: 8, Pages: 779-791
ISSN:1476-4679
DOI:10.1038/ncb2994
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncb2994
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncb2994
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Author Notes:Norman Ertych, Ailine Stolz, Albrecht Stenzinger, Wilko Weichert, Silke Kaulfuß, Peter Burfeind, Achim Aigner, Linda Wordeman and Holger Bastians
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Summary:Chromosomal instability (CIN) is defined as the perpetual missegregation of whole chromosomes during mitosis and represents a hallmark of human cancer. However, the mechanisms influencing CIN and its consequences on tumour growth are largely unknown. We identified an increase in microtubule plus-end assembly rates as a mechanism influencing CIN in colorectal cancer cells. This phenotype is induced by overexpression of the oncogene AURKA or by loss of the tumour suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers. Increased microtubule assembly rates are associated with transient abnormalities in mitotic spindle geometry promoting the generation of lagging chromosomes and influencing CIN. Reconstitution of proper microtubule assembly rates by chemical or genetic means suppresses CIN and thereby, unexpectedly, accelerates tumour growth in vitro and in vivo. Thus, we identify a fundamental mechanism influencing CIN in cancer cells and reveal its adverse consequence on tumour growth.
Item Description:Gesehen am 07.09.2020
Physical Description:Online Resource
ISSN:1476-4679
DOI:10.1038/ncb2994

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