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1.  Novel functions for Rab GTPases in multiple aspects of tumour progression 
Biochemical Society Transactions  2012;40(Pt 6):1398-1403.
Rab GTPases are master regulators of intracellular trafficking and, in recent years, their role in the control of different aspects of tumour progression has emerged. In the present review, we show that Rab GTPases are disregulated in many cancers and have central roles in tumour cell migration, invasion, proliferation, communication with stromal cells and the development of drug resistance. As a consequence, Rab proteins may be novel potential candidates for the development of anticancer drugs and, in this context, the preliminary results obtained with an inhibitor of Rab function are also discussed.
doi:10.1042/BST20120199
PMCID: PMC3554041  PMID: 23176488
cancer; exosome; invasion; migration; Rab GTPase; tumour microenvironment; CAF, cancer-associated fibroblast; ECM, extracellular matrix; EGFR, epidermal growth factor receptor; GAP, GTPase-activating protein; GEF, guanine-nucleotide-exchange factor; MDR, multidrug resistance; miRNA, microRNA; MMP, matrix metalloproteinase; MT1-MMP, membrane-type 1 MMP; P-gp, P-glycoprotein; RabGGTase, Rab geranylgeranyltransferase; RCP, Rab-coupling protein; Shh, Sonic Hedgehog
2.  Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment 
Journal of Cell Science  2012;125(7):1652-1656.
Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
doi:10.1242/jcs.100438
PMCID: PMC3346826  PMID: 22375060
Rab27a; Chemotaxis; Cell migration; Neutrophil; Uropod
3.  The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA 
The Journal of Cell Biology  2008;181(6):985-998.
Invadopodia are actin-based membrane protrusions formed at contact sites between invasive tumor cells and the extracellular matrix with matrix proteolytic activity. Actin regulatory proteins participate in invadopodia formation, whereas matrix degradation requires metalloproteinases (MMPs) targeted to invadopodia. In this study, we show that the vesicle-tethering exocyst complex is required for matrix proteolysis and invasion of breast carcinoma cells. We demonstrate that the exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. Interaction between IQGAP1 and the exocyst is necessary for invadopodia activity because enhancement of matrix degradation induced by the expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We further show that the exocyst and IQGAP1 are required for the accumulation of cell surface membrane type 1 MMP at invadopodia. Based on these results, we propose that invadopodia function in tumor cells relies on the coordination of cytoskeletal assembly and exocytosis downstream of Rho guanosine triphosphatases.
doi:10.1083/jcb.200709076
PMCID: PMC2426946  PMID: 18541705

Results 1-3 (3)