ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation

Koubek, Emily J.; Santy, Lorraine C.

doi:10.1080/21541248.2016.1219186

Cited by 9 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5g, h). These results are similar to previous findings in EGF-stimulated breast cancer cells, serum-stimulated glioma cells, and HGF-stimulated MDCK cells [52–54]. Seeing that ARNO is the only Arf6-specific GEF highly expressed in liver cancer tissues (Figs.…”

Section: Discussionsupporting

confidence: 92%

Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundAdhesion molecules distributed on the cell-surface depends upon their dynamic trafficking that plays an important role during cancer progression. ADP-ribosylation factor 6 (Arf6) is a master regulator of membrane trafficking. CD147, a tumor-related adhesive protein, can promote the invasion of liver cancer. However, the role of Arf6 in CD147 trafficking and its contribution to liver cancer progression remain unclear.MethodsStable liver cancer cell lines with Arf6 silencing and over-expression were established. Confocal imaging, flow cytometry, biotinylation and endomembrane isolation were used to detect CD147 uptake and recycling. GST-pull down, gelatin zymography, immunofluorescence, cell adhesion, aggregation and tight junction formation, Transwell migration, and invasion assays were used to examine the cellular phenotypes. GEPIA bioinformatics, patient’s specimens and electronic records collection, and immunohistochemistry were performed to obtain the clinical relevance for Arf6-CD147 signaling.ResultsWe found that the endocytic recycling of CD147 in liver cancer cells was controlled by Arf6 through concurrent Rab5 and Rab22 activation. Disruption of Arf6-mediated CD147 trafficking reduced the cell-matrix and cell-cell adhesion, weakened cell aggregation and junction stability, attenuated MMPs secretion and cytoskeleton reorganization, impaired HGF-stimulated Rac1 activation, and markedly decreased the migration and invasion of liver cancer cells. Moreover, high-expression of the Arf6-CD147 signaling components in HCC (hepatocellular carcinoma) was closely correlated with poor clinical outcome of patients.ConclusionsOur results revealed that Arf6-mediated CD147 endocytic recycling is required for the malignant phenotypes of liver cancer. The Arf6-driven signaling machinery provides excellent biomarkers or therapeutic targets for the prevention of liver cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Arf6 may affect Rac1 activation by several mechanisms such by 1) affecting phosphoinositide metabolism 52,53 which can regulate exchange factors for Rac1, 2) by releasing cytoplasmic Rac1 from Arfaptin, 54,55 3) by recruiting a Rac1 exchange factor (GEF), 56 or 4) by affecting a Rac1GEF that associated with the Arf GAPs. [57][58][59] In contrast, the effect of GIT2 on Rac1, Cdc42 and adhesion stability was independent of Arf6. The GIT-binding partner, b-PIX, is a Rac1GEF known to regulate adhesion dynamics and was considered as a potential mechanism by which GIT2 controlled Rac1GTP levels.…”

Section: Arf Gaps That Affect Integrin Adhesion Complexesmentioning

confidence: 94%

Arf GAPs: A family of proteins with disparate functions that converge on a common structure, the integrin adhesion complex

et al. 2017

View full text Add to dashboard Cite

ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration. Understanding the role of Arf GAPs in the regulation of integrin adhesion complexes is relevant to understanding normal physiology and cancer. In this review, we will discuss the contribution of the Arf GAP family members to the regulation of integrin adhesion complexes, examining the diverse mechanisms by which they control integrin adhesion complex formation, maturation and dissolution. GIT1 and ARAP2 serve as GAPs for Arf6, regulating Rac1 and other effectors by mechanisms still being defined. In contrast, GIT2 regulates Rac1 independent of Arf6. AGAP2 binds to and regulates focal adhesion kinase (FAK). ARAP2 and ACAP1, both Arf6 GAPs, regulate membrane trafficking of integrins through different endocytic pathways, exerting opposite effects on focal adhesions. ASAP1 not only regulates actin cytoskeleton remodeling through its interaction with nonmuscle myosin 2A, but is also important in integrin recycling. These examples illustrate the diversity and versatility of Arf GAPs as regulators of integrin adhesion complex structure and function.

show abstract

“…For example, the Arf family GTPase ARL4A targets ELMO–DOCK1 to membranes to activate RAC1-mediated membrane ruffling ( Patel et al, 2011 ). In addition, DOCK1 forms a complex with the ARF6 GEF cytohesin 2 and the adaptor protein GRASP, which facilitates recruitment of DOCK1 to the plasma membrane and promotes RAC1-dependent cell migration ( White et al, 2010 ; Koubek and Santy, 2016 ). These results show how important Arf-mediated membrane trafficking is for spatial activation of RAC1 at the plasma membrane.…”

Section: Gef Complexesmentioning

confidence: 99%