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
Cell migration, focal adhesion, integrin, Rab5.
Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Calle Sergio Livingstone P. 943, Independencia, Independencia, Santiago, Chile.