Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells

Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for -actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that -actin plays a role in mitosis. Herein, we investigated the effect of -actin in mitosis and demonstrated that -actin is important in the distribution of -actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of -actin depletion was replicated with a range of mitotic inhibitors, suggesting that -actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of -actin enhanced centrosome amplification in cancer cells and caused a significant delay in prometaphase/metaphase. This prolonged prometaphase/metaphase arrest was due to mitotic defects such as uncongressed and missegregated chromosomes, and correlated with an increased presence of mitotic spindle abnormalities in the -actin depleted cells. Collectively, these results demonstrate a previously unknown role for -actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity.