Rab25 in cancer: a brief update

Abstract

Derailed endocytosis is a hallmark of cancer. The endocytic pathway, as demonstrated by our laboratory, is a frequent target of genomic aberrations in cancer and plays a critical role in the maintenance of cellular polarity, stem cell function, bioenergetics, proliferation, motility, invasion, metastasis, apoptosis and autophagy. The Rab GTPases, along with their effectors, are critical regulators of this endocytic machinery and can have a huge impact on the cellular itinerary of growth and metabolism. Rab25 is an epithelial-cell-specific member of the Rab GTPase superfamily, sharing close homology with Rab11a, the endosomal recycling Rab GTPase. RAB25 has been implicated in various cancers, with reports presenting it as both an oncogene and a tumour-suppressor gene. At the cellular level, Rab25 was shown to contribute to invasiveness of cancer cells by regulating integrin trafficking. Recently, our laboratory uncovered a critical role for Rab25 in cellular energetics. Assimilating all of the existing evidence, in the present review, we give an updated overview of the complex and often context-dependent role of Rab25 in cancer.

Rab Proteins and the Compartmentalization of the Endosomal System

“…Rab4 regulates the recycling of integrins, receptors, ubiquitin ligases, and other transport machinery (Arjonen et al 2012;Cheng et al 2013;Cui and Zhang 2013). Rab11 isoforms and their downstream effectors have critical roles in cell polarity, and defects underlie cancer, gastrointestinal, and degenerative disease (for reviews, see Jing and Prekeris 2009;Kelly et al 2012;Mitra et al 2012). Rab9 regulates the recycling of cargo (mannose-6-phosphate receptor) from late endosomes to the Golgi complex (Lombardi et al 1993;McGourty et al 2012;Dong et al 2013).…”

Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis

“…14). The context-dependent role of Rabs to serve either as an oncoprotein or tumour suppressor may be owing in part to the interaction with different effectors in various tumours 30 .…”

Cyclophilin function in Cancer; lessons from virus replication

“…Certain members including Rab25 acts as both an oncogene and a tumoursuppressor gene [157,158]. Accelerated cell migration induced by upregulated Rab11 and Rab25 is associated with increased vesicular transport efficiency in the inner cell compartment and at the plasma membrane [159].…”