Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Shaughnessy, Ronan; Échard, Arnaud

doi:10.1111/tra.12546

Cited by 37 publications

(29 citation statements)

References 84 publications

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“…RAB GTPases are critical regulators of membrane trafficking, and mediate many biological processes of which dysregulation may lead to disease ( 41 – 44 ). Recently, they were identified as being important stimuli for tumorigenesis ( 45 – 47 ). For example, RAB1 serves as a significant mediator of endoplasmic reticulum-to-Golgi transport, which regulates cellular function and is linked to different cellular signaling pathways such as nutrient signaling, Notch signaling, and autophagy ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

et al. 2018

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Background: Gastric cancer (GC), one of the most common cancers worldwide, is highly malignant and fatal. Ras-related protein in brain 31 (RAB31), a member of the RAB family of oncogenes, participates in the process of carcinogenesis and cancer development; however, its role in GC progression is unknown.Methods: In our study, 90 pairs of tissue microarrays were used to measure the levels of RAB31 protein by immunochemistry, and 22 pairs of fresh tissue were used to measure the levels of RAB31 mRNA by quantitative PCR. We also investigated the effects of RAB31 on tumor growth both in vitro and in vivo.Results: RAB31 was overexpressed in GC tissues, and its overexpression predicted poor survival in patients. In a nude mouse model, depletion of RAB31 inhibited tumor growth. In vitro, silencing of RAB31 suppressed cell viability, promoted cell cycle arrest, enhanced apoptosis, and affected the expression of cell cycle and apoptotic proteins; these effects were mediated by glioma-associated oncogene homolog 1 (GLI1). Co-immunoprecipitation and immunofluorescence assays confirmed that RAB31 interacted with GLI1. In addition, luciferase reporter assays and Western blotting showed that microRNA-30c-2-3p modulated the RAB31/GLI1 pathway by targeting the 3′-untranslated region of RAB31.Conclusions: Collectively, these data show that RAB31 is regulated by microRNA-30c-2-3p, and functions as an oncogene in GC tumorigenesis and development by interacting with GLI1. Therefore, targeting the miR-30c-2-3p/RAB31/GLI1 axis may be a therapeutic intervention for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

et al. 2018

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“…Whereas Rab35 functions during early step of endosomal recycling, EHD1 is required for late endosomal scission events (Kouranti et al, 2006; Klinkert and Echard, 2016; Cauvin et al, 2016). Even though Rab35 functions’ in cell migration and adhesion vary according to the cell types or migration assays, it emerges as a pivotal component during cancer progression for receptor presentation, actin dynamics and cell polarity (Shaughnessy and Echard, 2018; Corallino et al, 2018). A link between Rab35 and RhoA was mentioned previously although not clearly demonstrated nor with any apparent impact (Chevallier et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Endosomal spatio-temporal modulation of the cortical RhoA zone conditions epithelial cell organization

Gaston

Beco

Doss

et al. 2020

Preprint

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SummaryAt the basis of cell shape and behavior, actomyosin organization and force-generating property are widely studied, however very little is known about the regulation of the contractile network in space and time. Here we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility, and we show that it is required for the maturation of stress fibers and frontrear polarity acquisition at the single cell level. There, EpCAM ensures the remodeling of a transient active RhoA zone in the cortex of spreading epithelial cells. GTP-RhoA follows the endosomal pathway mediated by Rab35 and EHD1, where it co-evolves together with EpCAM. In fact, EpCAM balances GTP-RhoA turnover in order to tune actomyosin remodeling for cell shape, polarity and mechanical property acquisition. Impairment of GTP-RhoA endosomal trafficking either by EpCAM silencing or Rab35 / EHD1 mutant expression prevents correct myosin-II activity, stress fiber formation, and ultimately cell polarization. Collectively, this work shows that the coupling of EpCAM/RhoA co-trafficking to actomyosin rearrangement is critical for spreading, and advances our understanding of how biochemical and mechanical properties can be coupled for cell plasticity.

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“…Rab35 is localized predominantly to both the plasma membrane and endosomes [19] and has been implicated in regulating a variety of processes including vesicle trafficking, endosome dynamics, cytokinesis, signaling and actin remodeling [22,60,61]. In adipocytes, Rab35 regulates trafficking of the glucose transporter isoform 4 (GLUT4) in response to insulin.…”

Section: Rab35mentioning

confidence: 99%

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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Rab35 GTPase and cancer: Linking membrane trafficking to tumorigenesis

Cited by 37 publications

References 84 publications

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

Endosomal spatio-temporal modulation of the cortical RhoA zone conditions epithelial cell organization

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

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