Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-08

AUTHORS

Norman Ertych, Ailine Stolz, Albrecht Stenzinger, Wilko Weichert, Silke Kaulfuß, Peter Burfeind, Achim Aigner, Linda Wordeman, Holger Bastians

ABSTRACT

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. More... »

PAGES

779-791

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb2994

DOI

http://dx.doi.org/10.1038/ncb2994

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039772886

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24976383


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