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Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells.

TitleIncreased microtubule assembly rates influence chromosomal instability in colorectal cancer cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsErtych N, Stolz A, Stenzinger A, Weichert W, Kaulfuß S, Burfeind P, Aigner A, Wordeman L, Bastians H
JournalNature cell biology
Date Published2014 Aug
KeywordsAurora Kinase A, BRCA1 Protein, Caco-2 Cells, Cell Line, Tumor, Checkpoint Kinase 2, Chromosomal Instability, Gene Expression, Chromosome Segregation, Colorectal Neoplasms, Genes, Tumor Suppressor, HCT116 Cells, HT29 Cells, Humans, Microtubules, Models, Biological, Oncogenes, Spindle Apparatus

<p>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.</p>

Alternate JournalNat. Cell Biol.