On the role of Rab5 in cell migration.

Uncontrolled endosome trafficking is a common feature of certain cancer cells, which has been acknowledged during the last decade. Migration and invasiveness of metastatic tumor cells are both regulated by components of the endocytic machinery, including Rab proteins. Rab GTPases are essential in processes of endosome fusion, as well as targeting, tethering and transport along the cytoskeleton. In addition to this canonical role, some Rabs depict other functions, such as controlling cell proliferation, apoptosis, adhesion and motility. Here, we review our current knowledge on the role of Rab5, a key regulator of early endosome dynamics, in migration of normal and tumor cells. Rab5 promotes cell migration in vitro and in vivo by mechanisms described at different levels. One such mechanism is by controlling the rates of integrin internalization and recycling, thereby affecting its activation and availability at the cell surface. On the other hand, Rab5 promotes focal adhesion disassembly and modulates downstream pathways of integrin signaling, involving proteins such as Ras and Rho family GTPases. In this context, identification of upstream regulators and downstream effectors of Rab5, and their study represents a big challenge in order to understand how cancer cells depend on endosome control, in order to acquire more aggressive traits that lead to metastatic disease.