Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. Integrin-mediated adhesions, in conjunction with the actin cytoskeleton, regulate cell fate and identity and allow cells to migrate and invade the surrounding extra-cellular matrix (ECM). Tight control over integrin mediated adhesion and signalling is paramount for normal cell function and is perturbed in almost every step of cancer progression. Our long-standing interest is in uncovering cancer relevant integrin-associated proteins and signalling networks. We have used RNAi screens to identify new proteins implicated in the regulation of integrin activity, integrin traffic, cell migration and metastasis. We are continuing this work by 1) investigating in mechanistic detail adhesion regulating protein networks using proximal-biotinylation, by 2) developing FRET-based probes to map the spatiotemporal regulation of integrin signalling under different conditions, by 3) screening for cell response to varying ECM compositions.