Cell migration is fundamental in the control of embryonic morphogenesis, tissue homeostasis, repair and inflammatory responses. Consequently, inappropriate migratory movements can result in autoimmune diseases, defective wound repair, or tumor cell metastasis. Cancer cells migrate alone or in small groups to spread from the primary tumour and are able to migrate to distal organs where they can continue to proliferate to form a second tumor mass. Cancer cell migration is regulated by adhesion signalling to drive dynamic actin remodelling. Fascin is an actin-bundling protein that is low or absent in normal human epithelia; its up-regulation correlates with poor prognosis in human carcinomas. Fascin localizes to and stabilizes actin-rich protrusions to promote cell migration. We have previously shown that the actin-bundling and pro-migratory properties of fascin are in part regulated by protein kinase C and the small GTPase Rac. However, very little is known about other regulators of fascin function or activity. Through a mass spec screen we have identified the nuclear envelope protein nesprin-1 as a novel binding partner for fascin. Our preliminary data supports a role for this complex in regulating nuclear shape in cells invading in 3D matrices. We hypothesise that this novel complex acts to control nuclear rigidity and plasticity, thus enabling tumour cells to navigate through complex tissues during invasion. Using a combination of biochemical and state-of-the-art microscopy approaches we aim to characterize the nesprin-fascin interaction further at the molecular level and to determine the upstream regulators responsible for dictating assembly of the complex. We will also define the role of the nesprin-fascin interaction in regulating nuclear shape, actin assembly and cell invasion in 3D matrices. Data arising from this study will provide important novel insight into the regulation of fascin and targets for future design of therapies to target invasive tumour cells.