Keep calm and carry on with extra centrosomes

Abstract

Precise chromosome segregation during mitosis is a vital event orchestrated by formation of bipolar spindle poles. Supernumerary centrosomes, caused by centrosome amplification, deteriorates mitotic processes, resulting in segregation defects leading to chromosomal instability (CIN). Centrosome amplification is frequently observed in various types of cancer and considered as a significant contributor to destabilization of chromosomes. This review provides a comprehensive overview of causes and consequences of centrosome amplification thoroughly describing molecular mechanisms. Abstract: Aberrations in the centrosome number and structure can readily be detected at all stages of tumor progression and are considered hallmarks of cancer. Centrosome anomalies are closely linked to chromosome instability and, therefore, are proposed to be one of the driving events of tumor formation and progression. This concept, first posited by Boveri over 100 years ago, has been an area of interest to cancer researchers. We have now begun to understand the processes by which these numerical and structural anomalies may lead to cancer, and vice-versa: how key events that occur during carcinogenesis could lead to amplification of centrosomes. Despite the proliferative advantages that having extra centrosomes may confer, their presence can also lead to loss of essential genetic material as a result of segregational errors and cancer cells must deal with these deadly consequences. Here, we review recent advances in the current literature describing the mechanisms by which cancer cells amplify their centrosomes and the methods they employ to tolerate the presence of these anomalies, focusing particularly on centrosomal clustering.