Function and regulation of Rab GTPases in cancers

Abstract The Rab small GTPases are characterized by the distinct intracellular localization and modulate various endocytic, transcytic and exocytic transport pathways. Rab proteins function as scaffolds that connect signaling pathways and intracellular membrane trafficking processes through the recruitment of effectors, such as tethering factors, phosphatases, motors and kinases. In different cancers, Rabs play as either an onco-protein or a tumor suppressor role, highly dependending on the context. The molecular mechanistic research has revealed that Rab proteins are involved in cancer progression through influences on migration, invasion, metabolism, exosome secretion, autophagy, and drug resistance of cancer cells. Therefore, targeting Rab GTPases to recover the dysregulated vesicle transport systems may provide potential strategy to restrain cancer progression. In this review, we discuss the regulation of Rab protein level and activity in modulating pathways involved in tumor progression, and propose that Rab proteins may serve as a prognostic factor in different cancers. Graphical Abstract • Rab GTPases together with the cognate effectors coordinates the dynamics of trafficking pathway and ensures the spatiotemporal regulation of vesicle trafficking. • Functional impairments of the regulatory network of vesicle trafficking are associated with tumorigenesis. • Rab proteins play oncogenic or tumor suppressor roles in different cancers depending on context.