Hold the centrosomes
R. Basto et al., “Centrosome amplification can initiate tumorigenesis in flies,” Cell, 133:1032–42, 2008. (Cited in 32 papers)
Tumor cells display both chromosomal instability and centrosome amplification, in which they have extra copies of the organelles that orchestrate the movement of microtubules and the progression through the cell cycle. But last year, a group led by researchers at the Gurdon Institute in the United Kingdom found that centrosome amplification alone is enough to incite tumor growth.
The missing step:
Cell biologist Jordan Raff and his colleagues developed a line of Drosophila that had extra centrosomes in 60% of their cells but largely normal chromosomes. “It was a big deal that they separated centrosome amplification from chromosome abnormalities,” says William Saunders, a University of Pittsburgh cell biologist who was not involved with the...
“The first big surprise was that centrosome amplification did not create large-scale chromosome instability,” Raff says. He also never expected to uncover the study’s main finding. “Personally, I never thought that centrosome amplification on its own would be enough to form tumors,” says Raff, now at the University of Oxford.
Unlike Raff, David Pellman, a Harvard cell biologist, recently found that centrosome amplification does cause widespread chromosomal instability, which he chocks up to errors in microtubule attachment during cell division (Nature, 460: 279–83, 2009). Saunders says that Pellman’s and Raff’s findings “may not be incompatible,” and the tumorigenesis in Raff’s flies could stem from this low-level of chromosome instability, not just centrosome amplification.
|Proteins involved in centrosome duplication|
|C. elegans:||ZYG-1, SAS-4, SAS-5, SAS-6|
|Drosophila:||Ana3, Sak, Ana1, Rcd1, Rcd2, DSas-6, emb, D-Sas4, Ana2|