Centrosome amplification is associated with cancer, but it remains unclear how multiple centrosomes may affect tumorigenesis. Godinho, Pellman and colleagues have revealed that supernumerary centrosomes confer an invasive behaviour to epithelial cells in 3D culture, through a mechanism involving Rac1 activation (Nature 510, 167–171; 2014).

Overexpression of polo-like kinase 4 (Plk4) was used to induce centrosome amplification in the epithelial cell line MCF10A. The authors observed that this resulted in invasive protrusions in 3D culture and collective migration in an organotypic culture system. Centrosome amplification is known to lead to chromosome missegregation and aneuploidy, but as aneuploidy induced by other means did not result in invasion, the authors concluded that aneuploidy per se is not responsible for the phenotype. Instead they observed that cell–cell contacts were disrupted, cells were scattered, and the position and size of cell–cell junctions altered. Rac1 activation is known to cause similar phenotypes, and, using biochemical methods as well as a Rac1 biosensor, the authors found that centrosome amplification did indeed induce Rac1 activation. Importantly, Rac1 inhibition partly rescued the cell–cell adhesion effects and blocked the formation of invasive acini induced by centrosome amplification. Previous work had suggested that dynamic microtubules may influence Rac1 activation, and the authors found increased centrosomal γ-tubulin levels and microtubule nucleation associated with supernumerary centrosomes. Furthermore, depletion of CEP192, a centrosomal protein needed for interphase γ-tubulin recruitment, could prevent Rac1 activation and disrupt invasion induced by supernumerary centrosomes. Thus, in cells with extra centrosomes, increased centrosomal microtubule nucleation leads to Rac1 activation, disruption of cell–cell contacts, and invasive behaviour.

Although the authors note that centrosome amplification is likely to have other effects contributing to tumorigenesis, this study offers insight into how extra centrosomes can induce the invasive behaviour associated with aggressive tumours.