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Review
. 2016 Oct 6;23(1):70.
doi: 10.1186/s12929-016-0287-7.

Rab-mediated vesicle trafficking in cancer

Hong-Tai Tzeng  1 , Yi-Ching Wang  2   3
Affiliations
Review

Rab-mediated vesicle trafficking in cancer

Hong-Tai Tzeng et al. J Biomed Sci. .

Abstract

A large group of small Rab GTPases which mediate secretory and endosomal membrane transport, as well as autophagosome biogenesis, are essential components of vesicle trafficking machinery. Specific Rab protein together with the cognate effectors coordinates the dynamics of trafficking pathway and determines the cargo proteins destination. Functional impairments of Rab proteins by mutations or post-translational modifications disrupting the regulatory network of vesicle trafficking have been implicated in tumorigenesis. Therefore, the vesicle transport regulators play essential roles in the mediation of cancer cell biology, including uncontrolled cell growth, invasion and metastasis. The context-dependent role of the same Rab to act as either an oncoprotein or tumor suppressor in different cancers is found. Such discrepancies may be due in part to the interaction of specific Rab protein with different effectors or cargos in various tumors. Here, we review recent advances in the roles of Rab GTPases in communicating with other effectors in tumor progression. In this review, we also emphasize dysregulation of Rab-mediated membrane delivery shifting normal cell behaviors toward malignancy. Thus, recovery of the dysregulated vesicle trafficking systems in cancer cells may provide future directions for potential strategy to restrain tumor progression.

Keywords: Cancer; Effector; Rab protein; Vesicle trafficking.

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Figures

Fig. 1
Fig. 1
Schematic diagram showing the Rab proteins-mediated vesicular transport and signaling pathways in tumorigenesis. Rab family proteins play key roles in regulating cellular membrane trafficking including endocytosis, exocytosis, exosome secretion as well as vesicles delivery between organelles. All of these vesicles dynamics affects cellular physiology. Dysregulation of oncogenic Rabs at the protein levels or activity such as Rab1, Rab25 and Rab35 exerts tumor-promoting properties such as anti-apoptosis, increase in proliferation, invasion and migration through activation of various signaling pathways. For example, Rab2A facilitates Erk1/2 activation and thus leads to Zeb1 upregulation and β-catenin nuclear translocation, then promotes tumor initiation. In contrast, malfunction of tumor suppressor Rabs promotes oncogenesis and tumor progression. For example, Rab37 delivers its cargo TIMP1 to inhibit MMP9 activity leading to suppression of tumor motility, while loss of Rab37-mediated TIMP1 secretion promotes tumor metastasis. Arrows indicate vesicular movement regulated by Rab proteins. Thick arrows represent Rabs-mediated signaling pathways involved in tumorigenesis and tumor suppression. Note that some organelles and vesicles are relatively enlarged to emphasize the pathways involved
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