The ESCRT machinery regulates degradative cargo sorting and cytokinesis, functions that when dysregulated lead to aberrant signalling and failures in cell division. It is possible that these failures may lead to oncogenesis and some cancers have recently been discovered in which ESCRT-components have been lost. Thus proposal seeks RCDF support to examine whether this machinery functions in a tumour suppressor role. I will analyse the contribution various ESCRT-components make to preventing cellular transformation and will map the molecular requirements within these proteins that supply this phenotype. In parallel, I will separate the contributions made to this tumour suppressor function by both cytokinetic and endosomal sorting aspects of ESCRT-biology. Using advanced imaging techniques, I will examine how this machinery is assembled and regulated, both in the context of endosomal sorting and cytokinesis. Additionally, I seek to understand the contribution of both intracellular traffic king and ESCRT-mediated receptor degradation to metastasis using the CXCR4/SDF1a axis as a model system. Finally, using CXCR4 as a model cargo, I will use genome-wide siRNA-based screens to discover new regulators of CXCR4 trafficking with particular focus on discovering novel regulators of its degradative sorting and will examine how these proteins influence chemotaxis and metastasis of cancer cells.