Establishing the role of centrosome amplification in tumorigenesis

A wealth of correlative evidence points to a role of centrosome amplification in the development of a wide array of cancer. However a direct test of this hypothesis has yet to be achieved in a vertebrate system due to difficulties in generating centrosome amplification in the absence of direct effects on oncogenes, tumor suppressor genes or cellular ploidy. Plk4’s only known function is in regulating centrosome copy number and therefore, increasing Plk4 levels provides a mechanism to create supernumerary centrosomes in vivo in the absence of additional defects. Moreover, centrosomes are stable structures and thus, even a transient increase in Plk4 levels leads to irreversible centrosome amplification. 

 

To explore the role of centrosome amplification contributes to the development of cancer, we have created a novel mouse model in which Plk4 levels can be transiently increased in vivo to promote centrosome amplification. We are now using this model foundation for further in vivo studies aimed at investigating the role of centrosome amplification in the development of cancer.