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  • Review Article
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Centrosome aberrations: cause or consequence of cancer progression?

Nature Reviews Cancer volume 2, pages 815–825 (2002)Cite this article

Key Points

  • The centrosome nucleates microtubules; it is important for cell shape, motility and division. During S phase of the cell cycle, the single centrosome that is present in a G1-phase cell is duplicated. The two centrosomes then set up the poles of the mitotic spindle and each incipient daughter cell receives one centrosome.

  • The duplication and segregation cycles of centrosomes and chromosomes need to be coordinated to avoid chromosome missegregation or ploidy changes. The retinoblastoma pathway has been identified as one important link between centrosome duplication and chromosome replication.

  • Many tumours display numerical and structural centrosome aberrations. Extra copies of centrosomes could, in principle, arise through overduplication within a single cell cycle, through aborted cell division, cell fusion or de novo genesis. A growing body of evidence points to aborted division as an important cause of excessive centrosome numbers.

  • Cells that lack a functional p53 pathway are proposed to acquire multiple centrosomes through failure of a G1-phase checkpoint that should eliminate cells after aborted division. However, it has also been argued that p53 regulates centrosome duplication.

  • Centrosome aberrations can give rise to chromosomal instability and altered tissue architecture. Importantly, centrosome aberrations and chromosomal instability are expected to enhance each other.

  • Most multipolar divisions cause severe chromosome missegregation and therefore constitute lethal events. Occasionally, however, they might give rise to cells with chromosomal compositions that favour survival in the microenvironment of the tumour. In tumour cells, genes that are involved in alternative mechanisms for spindle formation might be upregulated or re-expressed. This might cause several centrosomes to coalesce and allow the formation of bipolar spindles, in spite of excessive centrosome numbers.

  • A better understanding of the origins and consequences of centrosome aberrations could lead to the development of novel diagnostic, prognostic or therapeutic approaches.

Abstract

Many human tumours show centrosome aberrations, indicating an underlying deregulation of centrosome structure, duplication or segregation. Centrosomes organize microtubule arrays throughout the cell cycle, thereby influencing both tissue architecture and the accuracy of chromosome segregation. But what are the origins of centrosomal abnormalities in tumours, and what impact do they have on the generation of invasive, genetically unbalanced cells during cancer progression?

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Figure 1: The cell cycle: a tale of two cycles.
Figure 2: Centrosomal abnormalities in human tumours.
Figure 3: Centrosome amplification.
Figure 4: The RB pathway and centrosome duplication.
Figure 5: Coalescence of centrosomes to two poles in a mitotic neuroblastoma cell.

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Acknowledgements

I thank F. Barr, T. Mayer, P. Meraldi, H. Silljé and C. Wilkinson for helpful comments on the manuscript and M. Bornens (Paris), M. Casenghi (Martinsried), S. Doxsey (Worcester) and W. Lingle (Rochester) for generously contributing material for the figures. My sincere apologies go to all authors whose primary work could not be cited due to space constraints.

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Authors and Affiliations

  1. Department of Cell Biology, Max Planck Institute of Biochemistry, Am Klopfersitz 18a, Martinsried, D-82152, Germany

    Erich A. Nigg

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  1. Erich A. Nigg
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DATABASES

Cancer.gov

bile duct cancer

brain cancer

breast cancer

cervical cancer

colon cancer

head and neck cancer

lung cancer

pancreatic cancer

prostate cancer

GenBank

E6

E7

HPV-16

LocusLink

AKAP450

Aurora-A

CDK2

C-NAP1

GADD45

kendrin

MDM2

ninein

p53

pericentrin

RAD6

RB

WAF1

FURTHER INFORMATION

Erich A. Nigg's web site

Mitelman Database of Chromosome Aberrations in Cancer

Mitosis World

Glossary

CYTOKINESIS

The process of cytoplasmic division.

SPINDLE

A dynamic bipolar array of microtubules that is assembled during mitosis and meiosis to segregate chromosomes.

ASTERS

Radial microtubule arrays with minus ends that are usually tethered to centrosomes (or assemblies of centrosomal proteins) and plus ends that extend towards the periphery.

CLEAVAGE PLANE

The plane of cell division — defined by the assembly of a contractile actomyosin ring at the cell cortex.

γ-TUBULIN RING COMPLEX

A γ-tubulin-containing multiprotein complex that acts as a ring-shaped template for microtubule nucleation in metazoan organisms.

ACENTRIOLAR BODIES

Assemblies of centrosomal proteins that can form in the absence of centrioles.

ORGANOTYPIC CULTURE

The in vitro maintenance and growth of tissue explants and multicellular cultures that mimic cell interactions within tissues.

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Nigg, E. Centrosome aberrations: cause or consequence of cancer progression?. Nat Rev Cancer 2, 815–825 (2002). https://doi.org/10.1038/nrc924

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  • DOI: https://doi.org/10.1038/nrc924

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