Targeting the Actin Cytoskeleton in Cancer Cell Biology

The Arp2/3 complex is a ubiquitous actin nucleator well-characterized activities in motility and cellular remodeling. The Arp2/3 complex also has relatively understudied roles in nuclear processes including DNA damage repair and cell division. We investigated the activity of the Arp2/3 complex in U2OS human osteosarcoma cells by exposing cells to CK666, a potent inhibitor of the Arp2/3 complex. Following Arp2/3 complex inhibition, cells accumulated DNA damage and significantly slowed their proliferation rate or arrested. Micronuclei were less common in Arp2/3-inhibited cells and were more likely to contain significant DNA damage. Treated cells also exhibited an overall decrease in nuclear content, most likely indicative of a G1 cell cycle arrest, and showed an insignificant increase in Lamin B1. This study confirmed the importance of the Arp2/3 complex in maintaining genome stability and clarified the roles of the Arp2/3 complex in nuclear processes