Cyclin A2 regulates symmetrical mitotic spindle formation and centrosome amplification in human colon cancer cells.

Colon cancer is one of the most fatal cancers in the United States, and is characterized by the presence of chromosomal instability (CIN), causes of which are largely unclear. Emerging evidence indicates that abnormal spindle geometry and supernumerary centrosomes lead to CIN in cells. However, if and how spindle geometry defects and centrosomes amplification occur in colon cancer remains unknown. Here we show that decrease in the cell cycle regulatory protein, cyclin A2, induces spindle geometry defects in colon cancer cells. In mechanistic studies, we found that cyclin A2 is located at the centrosomes, and its depletion reduces phosphorylation of EG5, which is important for centrosome localization and movement of duplicated centrosomes to opposite poles. We also found that cyclin A2 silencing leads to centrosome amplification in the cells. Collectively, these findings demonstrate previously unrecognized role for cyclin A2 in preventing centrosomal defects in colon cancer cells and provide insights into mechanisms that may potentially cause CIN in these tumors.