Cells inversely adjust the plasma membrane levels of integrins and cadherins 
during cell migration and cell-cell adhesion but the regulatory mechanisms that 
coordinate these trafficking events remain unknown. Here, we demonstrate that 
the small GTPase Rab35 maintains cadherins at the cell surface to promote 
cell-cell adhesion. Simultaneously, Rab35 supresses the activity of the GTPase 
Arf6 to downregulate an Arf6-dependent recycling pathway for β1-integrin and EGF 
receptors, resulting in inhibition of cell migration and attenuation of 
signaling downstream of these receptors. Importantly, the phenotypes of 
decreased cell adhesion and increased cell migration observed following Rab35 
knock down are consistent with the epithelial-mesenchymal transition, a feature 
of invasive cancer cells, and we show that Rab35 expression is suppressed in a 
subset of cancers characterized by Arf6 hyperactivity. Our data thus identify a 
key molecular mechanism that efficiently coordinates the inverse intracellular 
sorting and cell surface levels of cadherin and integrin receptors for cell 
migration and differentiation.