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Extra Centrosomes Can Drive Tumor Formation in Mice

Mice engineered to overproduce the organelles involved in cell division spontaneously develop malignancies.

Apr 1, 2017
Diana Kwon

OVERCROWDED: A cell with too many centrosomes (each with two centrioles; green), extra mitotic spindles (red), and abnormally segregated DNA (blue)BRAMWELL LAMBRUS, HOLLAND LAB

EDITOR'S CHOICE IN CANCER BIOLOGY

The paper
M.S. Levine et al., “Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals,” Dev Cell, 40:313-22, 2017.

Three’s a crowd
More than a century ago, the German biologist Theodor Boveri observed that cancer cells often had extra centrosomes, organelles essential for the segregation of chromosomes during mitosis. This raised a question that scientists have since puzzled over for decades:
Is centrosome amplification a cause or effect of cancer?

See "A Cellar's Cellular Treasure"

Chicken or egg
In 2008, researchers found the first compelling evidence that extra centrosomes could drive tumor formation in flies. However, subsequent studies in mice failed to replicate the results, leading some to question the universality of extra centrosomes’ effects.

Master regulator
In the latest study to investigate this link, Andrew Holland, a cancer researcher at Johns Hopkins University School of Medicine, and his colleagues genetically engineered mice to overexpress Polo-like kinase 4 (Plk4), the “master regulator” of centrosome copy number. They found that once the mice were around eight months old, they began to develop a variety of tumors, including lymphomas and sarcomas. This study is “an important, clear piece of evidence for a long-standing idea,” says David Pellman, a cell biologist at Harvard Medical School. Still, how much “chromosome segregation errors versus other effects of centrosome amplification [drives tumorigenesis] remains poorly understood.”

Sweet spots
Holland said he thinks his team’s experiment succeeded because they were able to reach the “sweet spot of instability,” given that too many centrosomes can be lethal. “It’s nice now that both fly and mouse show that if you amplify centrosomes you can promote tumorigenesis,” says the University of Oxford’s Jordan Raff, a coauthor of the 2008 study, “but it’s still not very clear how important that is for human cancers.”

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