Impact of Centrosome Aberrations on Chromosome Segregation and Tissue Architecture in Cancer

Abstract

Centrosomes determine the disposition of microtubule networks and thereby contribute to regulate cell shape, polarity, and motility, as well as chromosome segregation during cell division. Additionally, centrioles, the core components of centrosomes, are required for the formation of cilia and flagella. Mutations in genes coding for centrosomal and centriolar proteins are responsible for several human diseases, foremost ciliopathies and developmental disorders resulting in small brains (primary microcephaly) or small body size (dwarfism). Moreover, a long-standing postulate implicates numerical and/or structural centrosome aberrations in the etiology of cancer. In this review, we will discuss recent work on the role of centrosome aberrations in the promotion of genome instability and the disruption of tissue architecture, two hallmarks of human cancers. We will emphasize recent studies on the impact of centrosome aberrations on the polarity of epithelial cells cultured in three-dimensional spheroid models. Collectively, the results from these in vitro systems suggest that different types of centrosome aberrations can promote invasive behavior through different pathways. Particularly exciting is recent evidence indicating that centrosome aberrations may trigger the dissemination of potentially metastatic cells through a non-cell-autonomous mechanism.