γ-Tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells

Ryoko Kuriyama, Monica Bettencourt-Dias, Ingrid Hoffmann, Marc Arnold, Lisa Sandvig

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Cancer cells frequently induce aberrant centrosomes, which have been implicated in cancer initiation and progression. Human colorectal cancer cells, HCT116, contain aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. These cells also express unique centrosome-related structures associated with a subset of centrosomal components, including γ-tubulin, centrin and PCM1. During hydroxyurea treatment, these abnormal structures become more abundant and undergo a change in shape from small dots to elongated fibers. Although γ-tubulin seems to exist as a ring complex, the abnormal structures do not support microtubule nucleation. Several lines of evidence suggest that the fibers correspond to a disorganized form of centriolar microtubules. Plk4, a mammalian homolog of ZYG-1 essential for initiation of centriole biogenesis, is not associated with the γ-tubulin-specific abnormal centrosomes. The amount of Plk4 at each centrosome was less in cells with abnormal centrosomes than cells without γ-tubulin-specific abnormal centrosomes. In addition, the formation of abnormal structures was abolished by expression of exogenous Plk4, but not SAS6 and Cep135/Bld10p, which are downstream regulators required for the organization of nine-triplet microtubules. These results suggest that HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4.

Original languageEnglish (US)
Pages (from-to)2014-2023
Number of pages10
JournalJournal of cell science
Volume122
Issue number12
DOIs
StatePublished - Jun 15 2009

Keywords

  • Centrioles
  • Centrosomes
  • Cep135
  • HCT116 cells
  • Hydroxyurea
  • Nine-triplet microtubules
  • Plk4
  • SAS6
  • γ-tubulin

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