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  • Review Article
  • Published:

Centrosomes and cancer: revisiting a long-standing relationship

Key Points

  • Over a century ago, Theodor Boveri postulated that centrosome aberrations, which are prevalent in tumour cells, could cause cancer by promoting genome instability.

  • Centrosomes comprise centrioles plus surrounding pericentriolar material (PCM), and function as the major microtubule organizing centre (MTOC) of animal cells.

  • The canonical centrosome duplication cycle is tightly coupled to cell cycle progression, thus ensuring coordinated execution of DNA replication and centrosome duplication.

  • Cells with extra centrosomes can assemble a bipolar spindle owing to clustering mechanisms acting during mitosis, but undergo inaccurate chromosome segregation.

  • The presence of extra centrosomes can initiate tumour formation in Drosophila melanogaster, but not in the developing mammalian brain.

  • Centrosome aberrations could contribute to abnormal proliferation through other mechanisms, including by influencing spindle geometry, centriole inheritance in stem cell lineages, ciliary function or cell invasion.

Abstract

Over a century ago, centrosome aberrations were postulated to cause cancer by promoting genome instability. The mechanisms governing centrosome assembly and function are increasingly well understood, allowing for a timely reappraisal of this postulate. This Review discusses recent advances that shed new light on the relationship between centrosomes and cancer, and raise the possibility that centrosome aberrations contribute to this disease in different ways than initially envisaged.

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Figure 1: Hansemann and Boveri: pioneers at the turn of the nineteenth century.
Figure 2: Centriolar architecture.
Figure 3: Centrosome duplication cycle.
Figure 4: Four important steps of the centrosome duplication cycle.
Figure 5: Centriole number aberrations and spindle assembly.
Figure 6: Centrosomes and proliferation control: old and new ideas.

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Acknowledgements

The author is grateful to P. Guichard, V. Hamel, D. Hanahan and B. Wolf for their comments on the manuscript, as well as to P. Guichard and F. R. Balestra, then at the Gönczy laboratory, for contributing figure material. Apologies go to those authors whose work could not be mentioned owing to space limitations; with 1,812 PubMed entries that contain the words 'centrosome' and 'cancer' as of 30 May 2015, when this Review was submitted, unfortunately some aspects had to be neglected here. Work on different aspects of centrosome biology in the author's laboratory is supported by the Swiss Cancer League (KLS 3388-02-2014) and the European Research Council (AdG 340227).

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Glossary

Microtubule-organizing centre

(MTOC). Region of the cell, such as the centrosome, from which microtubules emanate.

Super-resolution light microscopy

Light microscopy approaches (for example, structured illumination microscopy (SIM), stimulated emission depletion (STED), and stochastic optical reconstruction microscopy (STORM)) that have a better resolution than the 250 nm diffraction limit of conventional optical microscopes.

Coiled-coil proteins

Proteins containing one or more coiled-coil domains, in which several α-helices are coiled together, often as dimers.

Plus-end-directed motor

A protein that uses the energy liberated by ATP hydrolysis to propel itself towards the plus end of a microtubule.

Hydroxyurea

A small molecule compound preventing the conversion of ribonucleotides to deoxyribonucleotides, thus inhibiting DNA synthesis and arresting cells in S phase.

Aphidicolin

A small compound that notably blocks the activity of DNA polymerases, thus arresting cells in early S phase.

Securin

A protein that maintains separase in its inactive state until the spindle assembly checkpoint has been satisfied at the metaphase to anaphase transition.

Spindle assembly checkpoint

(SAC). A multiprotein complex acting during mitosis to prevent the segregation of sister chromatids before they are attached to the microtubules emanating from the two spindle poles.

Minus-end-directed kinesin 14 motor

A protein that uses the energy liberated by ATP hydrolysis to propel itself towards the minus end of a microtubule.

Microcephaly

A clinical phenotype characterized by a small brain size.

Neurospheres

Culture systems of neural stem cells that enable investigators to study the ability of these cells to adopt proper collective architecture outside the animal.

Autosomal recessive primary microcephaly

(MCPH). A congenital disease characterized by a small brain size, thought to derive from defective asymmetric division in the ventricular zone during the development of the neocortex.

Cytotoxic T lymphocytes

(CTLs). A class of T lymphocytes that kill cancer cells as well as virally infected cells.

Natural killer cells

Cytotoxic cells of the innate immune system that have an important role in the killing of cancer cells and virally infected cells.

Stem cell niche

The microenvironment in which stem cells reside, and which contributes to proper maintenance of stem cell fate.

Axoneme

A microtubule-based structure with a ninefold symmetrical arrangement of microtubules templated by the mother centriole and located at the core of cilia and flagella.

Ciliopathies

Diseases resulting from the malfunction of the primary cilium; ciliopathies comprise a broad spectrum of phenotypic manifestations, including brain abnormalities, oral-facial deformities, obesity and renal defects.

Mitotic catastrophe

Cell death occurring during mitosis.

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Gönczy, P. Centrosomes and cancer: revisiting a long-standing relationship. Nat Rev Cancer 15, 639–652 (2015). https://doi.org/10.1038/nrc3995

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