Rab-mediated integrin trafficking at different stages of tumorigenesis

Integrins are the main mediators of cell-matrix interaction which play crucial roles in the definition of cell behaviour and fate by binding a great variety of extracellular ligands and activating different signalling cascades. Considering that many aspects of cell physiology are influenced by integrins, several distinct mechanisms have to cooperate in the fine regulation of the overall function of these receptors. Among them, endosomal trafficking is now emerging as an essential mechanism in the modulation of integrins expression on cell surface which is of critical importance for the dynamic regulation of integrin-mediated functions. The precise spatiotemporal control of endocytosis and recycling of these receptors back and forth the plasma membrane is ensured by Rab proteins, a large family of small GTPases involved in the regulation of each step of vesicle trafficking pathways. Emerging data indicate that alteration of integrin trafficking dynamics, resulting from the dysregulation of different Rabs, can substantially contribute to different stages of tumour development by favouring the acquisition of oncogenic properties such as enhanced migration and invasion.