Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells

Nat Cell Biol. 2014 Aug;16(8):779-91. doi: 10.1038/ncb2994. Epub 2014 Jun 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A / genetics*
  • BRCA1 Protein / genetics
  • Caco-2 Cells
  • Cell Line, Tumor
  • Checkpoint Kinase 2 / genetics*
  • Chromosomal Instability*
  • Chromosome Segregation / genetics
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression
  • Genes, Tumor Suppressor
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Microtubules / enzymology
  • Microtubules / genetics*
  • Microtubules / pathology
  • Models, Biological
  • Oncogenes
  • Spindle Apparatus / enzymology
  • Spindle Apparatus / genetics
  • Spindle Apparatus / pathology


  • BRCA1 Protein
  • BRCA1 protein, human
  • Checkpoint Kinase 2
  • AURKA protein, human
  • Aurora Kinase A
  • CHEK2 protein, human