Rab25 GTPase: Functional roles in cancer

Wang, Sisi; Hu, Chunhong; Wu, Fang; He, Shasha

doi:10.18632/oncotarget.19571

Cited by 42 publications

(46 citation statements)

References 68 publications

(131 reference statements)

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“…For instance, as it relates to exocytosis and cancer, dysregulation of the class of small GTPases and Rab effector proteins, such as Rab27a and Rab27b isoforms, Rab25, Rab40b, and Rabphilin, has been shown to promote tumor cell migration, invasion, and metastasis through disruption of membrane vesicle trafficking and docking (Gomi et al, 2007;Hendrix et al, 2010b;Shaughnessy and Echard, 2018;Tzeng et al, 2017;Tzeng and Wang, 2016;Wang et al, 2017). The soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors, soluble NSF attachment protein receptor (SNARE) proteins, and SNARE modulators have long been implicated in vesicle trafficking and fusion in synaptic nerves.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

Stephens

Osunsanmi

Sochacki

et al. 2019

Journal of General Physiology

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Altered regulation of exocytosis is an important mechanism controlling many diseases, including cancer. Defects in exocytosis have been implicated in many cancer cell types and are generally attributed to mutations in cellular transport, trafficking, and assembly of machinery necessary for exocytosis of secretory vesicle cargo. In these cancers, up-regulation of trafficking and secretion of matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme, is responsible for degrading the extracellular matrix, a necessary step in tumor progression. Using TIRF microscopy, we identified proteins associated with secretory vesicles containing MMP-9 and imaged the local dynamics of these proteins at fusion sites during regulated exocytosis of MMP-9 from MCF-7 breast cancer cells. We found that many regulators of exocytosis, including several Rab GTPases, Rab effector proteins, and SNARE/SNARE modulator proteins, are stably assembled on docked secretory vesicles before exocytosis. At the moment of fusion, many of these components are quickly lost from the vesicle, while several endocytic proteins and lipids are simultaneously recruited to exocytic sites at precisely that moment. Our findings provide insight into the dynamic behavior of key core exocytic proteins, accessory proteins, lipids, and some endocytic proteins at single sites of secretory vesicle fusion in breast cancer cells.

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Section: Introductionmentioning

confidence: 99%

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

Stephens

Osunsanmi

Sochacki

et al. 2019

Journal of General Physiology

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“…Multiple clinical findings support the role of Rab25 as a prognostic marker for patients with several types of cancers such as breast, ovarian and renal cancer [47]. Furthermore, Rab25 mRNA is increased in multiple other cancer types including ovarian, prostate, bladder, breast and liver cancers making it a highly relevant target for potential cancer therapies.…”

Section: Rab25mentioning

confidence: 82%

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

Krishnan

Golden

Woodward

et al. 2020

Cancers

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The Rab GTPase family of proteins are mediators of membrane trafficking, conferring identity to the cell membranes. Recently, Rab and Rab-associated factors have been recognized as major regulators of the intracellular positioning and activity of signaling pathways regulating cell growth, survival and programmed cell death or apoptosis. Membrane trafficking mediated by Rab proteins is controlled by intracellular localization of Rab proteins, Rab-membrane interactions and GTP-activation processes. Aberrant expression of Rab proteins has been reported in multiple cancers such as lung, brain and breast malignancies. Mutations in Rab-coding genes and/or post-translational modifications in their protein products disrupt the cellular vesicle trafficking network modulating tumorigenic potential, cellular migration and metastatic behavior. Conversely, Rabs also act as tumor suppressive factors inducing apoptosis and inhibiting angiogenesis. Deconstructing the signaling mechanisms modulated by Rab proteins during apoptosis could unveil underlying molecular mechanisms that may be exploited therapeutically to selectively target malignant cells.

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“…It recognizes a conserved motif found in the α-tails of all integrins (apart from α11) and regulates integrin endocytosis (Pellinen et al, 2006;Mai et al, 2011). RAB25, on the other hand, is expressed only in specific epithelial tissues and some carcinomas (Wang et al, 2017) and associates with the fibronectin-binding α5β1-integrin to drive its recycling (Caswell et al, 2007). Previous studies have shown the role of RAB13 in trafficking of receptors between trans-Golgi network and transferrinpositive recycling endosomes in epithelial cells (Nokes et al, 2008) and activation of RAB13 by guanine nucleotide exchange factor DENND2B on the plasma membrane has been linked to cancer cell migration and invasion (Ioannou et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

GGA2 and RAB13 promote activity-dependent β1-integrin recycling

Sahgal

Alanko

Icha

et al. 2018

Preprint

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β1-integrins mediate cell-matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes like cancer cell invasion. Here we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1integrin and its role in recycling of the active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion congruent with its ability to regulate the dynamics of active integrins.Using the proximity-dependent biotin identification (BioID) method, we identify two RAB family small GTPases, RAB13 and RAB10, associating with GGA2 and β1-integrin.Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, reduces integrin activity, in focal adhesions, and cell migration, similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic. 30 min after internalization 5 µm 5 µm 5 µm 0 min Active β1-integrin Active β1-integrin Active β1-integrin GFP Active β1-integrin GFP-RAB13 Active β1-integrin GFP-RAB11 Active β1-integrin Active β1-integrin Active β1-integrin Active β1-integrin GFP Active β1-integrin GFP-RAB13 Active β1-integrin GFP-RAB11

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Rab25 GTPase: Functional roles in cancer

Cited by 42 publications

References 68 publications

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

GGA2 and RAB13 promote activity-dependent β1-integrin recycling

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