Disruption of centrosome duplication control and induction of mitotic instability by the high-risk human papillomavirus oncoproteins E6 and E7

Abstract

Centrosome abnormalities and genomic instability are hallmarks of major human malignancies and have been implicated in malignant progression as well as therapy resistance. Since the etiology of most cancers is complex and incompletely understood, it is vital to utilize tumors which are caused by limited oncogenic stimuli to explore causes and consequences of centrosome aberrations in cancer cells. High-risk HPV-associated neoplasms are suitable model systems since only two viral oncoproteins, E6 and E7, are consistently overexpressed in HPV-associated cancers, for example, of the uterine cervix. HPV-16 E6 and E7 have been instrumental in a number of ways to better understand centrosome aberrations in cancer. Using these two oncoproteins, it has been shown that centrosome overduplication and centrosome accumulation are fundamentally different processes but can co-exist in a tumor. In this chapter we highlight the importance of HPV oncoproteins as tools to dissect basic cellular processes in human cancer and to provide a basis for novel translational approaches to prevent and treat cancer.