ArticleCancer cell2016
ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.
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Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94citing papers in PubMed
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Who cites it
94 citing papers in PubMed, 153 citations in OpenAlex.
- GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.Cancer research · 2026Article
- Rapid activation of ARF6 after RAF inhibition augments BRAFOncogene · 2026Article
- Recent advances in the molecular genetic mechanisms and immune microenvironment of uveal melanoma.Melanoma research · 2026Review
- ARF6 promotes the nuclear translocation of β-catenin to facilitate AFP deficiency-mediated metastasis in CTNNB1Cell biology and toxicology · 2026Article
- Network-based analysis reveals potential microRNA regulation of oncogenic pathways in SOX10-depleted uveal melanoma.Cellular and molecular life sciences : CMLS · 2026Article
- CD248 acts as a mechanosensory switch in fibroblast subsets to establish distinct pathological niches in renal fibrosis.Nature communications · 2026Article
- The small GTPase ARF6 regulates sphingolipid homeostasis and supports proliferation in acute myeloid leukemia.Haematologica · 2026Article
- Unraveling Novel Genetic Determinants of Thiopurine Response Via TWAS.Clinical pharmacology and therapeutics · 2026Article
- Endothelial Arf6 sustains capillary electrical signaling and cerebral blood flow through PIPbioRxiv : the preprint server for biology · 2025Article
- GNAQ mutation in primary spinal melanoma: illustrative case.Journal of neurosurgery. Case lessons · 2025Article
- Article
- Rapid activation of ARF6 after RAF inhibition augments BRAFV600E and promotes therapy resistance.Research square · 2025Article
- Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025Review
- Identification and validation of ARF6 for a potential prognostic biomarker of acute myeloid leukemia.Cancer cell international · 2025Article
- The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.Communications biology · 2025Article
- The cytoplasmic tail of IBV spike mediates intracellular retention via interaction with COPI-coated vesicles in retrograde trafficking.Journal of virology · 2025Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.Nature communications · 2024Article
- Review
- Targeting Recycling Endosomes to Potentiate mRNA Lipid Nanoparticles.Nano letters · 2024Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 2 countries.
Jae Hyuk YooDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
Dallas S ShiDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Allie H GrossmannDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA; ARUP Laboratories, University of Utah, Salt Lake City, UT 84112, USA.
Lise K SorensenDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA.
ZongZhong TongNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA; Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China.
Tara M MleynekDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA.
Aaron RogersDepartment of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
Weiquan ZhuDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA.
Jackson R RichardsDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
Jacob M WinterDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA.
Jie ZhuDepartment of Ophthalmology and Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Christine DunnNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA.
Ashok BajjiNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA; VioGen Biosciences LLC, Salt Lake City, UT 84119, USA.
Mark ShenderovichNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA; Mol3D Research LLC, Salt Lake City, UT 84124, USA.
Alan L MuellerNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA.
Scott E WoodmanDepartment of Melanoma Medical Oncology, Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77054, USA.
J William HarbourOcular Oncology Service, Bascom Palmer Eye Institute and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Kirk R ThomasDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Division of Hematology, Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA.
Shannon J OdelbergDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA; Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
Kirill OstaninNavigen Inc., 383 Colorow Drive, Salt Lake City, UT 84108, USA. Electronic address: kostanin@nvgn.com.
Dean Y LiDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA; ARUP Laboratories, University of Utah, Salt Lake City, UT 84112, USA; Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA; Department of Cardiology, VA Salt Lake City Health Care System, Salt Lake City, UT 84112, USA. Electronic address: dean.li@u2m2.utah.edu.
University of Utah · USNavigen (United States) · USARUP Laboratories (United States) · USAureoGen Biosciences (United States) · USSylvester Comprehensive Cancer Center · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Diego · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MUniversity of Utah Center for Clinical and Translational ScienceUL1TR001067 · NCATS · UNIVERSITY OF UTAH · PI DERE, WILLARD H., HESS, RACHEL · 2013 to 2017
$19.8MTranslational Research Skills Development CoreU54HL112311 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2012 to 2016
$12.9MTRAINING IN CARDIOVASCULAR RESEARCHT32HL007576 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stavros George Drakos, Robin M Shaw · 1985 to 2026
$10.6MUniversity of Utah Center for Clinical and Translational Science-UL1UL1TR000105 · NCATS · UNIVERSITY OF UTAH · PI MCCLAIN, DONALD A. · 2012 to 2013
$5.1MMOLECULAR PREDICTIVE TESTING IN OCULAR MELANOMAR01CA125970 · NCI · WASHINGTON UNIVERSITY · PI CORREA, ZELIA MARIA, HARBOUR, JAMES WILLIAM · 2006 to 2021
$4.9MNovel vascular guidance mechanismsR01HL077671 · NHLBI · UNIVERSITY OF UTAH · PI ZHU, WEIQUAN (WENDY) · 2004 to 2017
$4.3MOpposing Mechanisms of Stabilizing and Destabilizing ReceptorsR01HL084516 · NHLBI · UNIVERSITY OF UTAH · PI LI, DEAN YAW · 2007 to 2016
$3.0MIdentifying a nodal point for G alpha q signaling in eye diseaseR01CA202778 · NCI · UNIVERSITY OF UTAH · PI ODELBERG, SHANNON J · 2016 to 2020
$1.7MTargeting ARF6, A Convergence Point For Multiple Pathways of Diabetic RetinopathyR01EY025342 · NEI · UNIVERSITY OF UTAH · PI ZHU, WEIQUAN (WENDY) · 2015 to 2019
$1.7MThe Role of the Vasculature in the Pathogenesis of ArthritisR01AR064788 · NIAMS · UNIVERSITY OF UTAH · PI ODELBERG, SHANNON J · 2013 to 2017
$1.6MHigh Content Sceening for Hereditary Stroke SyndromeR01NS080893 · NINDS · UNIVERSITY OF UTAH · PI LI, DEAN YAW · 2013 to 2015
$975kNCATS NIH HHS UL1 TR000105NCATS NIH HHS UL1 TR001067NCI NIH HHS K08 CA188563NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA125970NCI NIH HHS R01 CA163970NCI NIH HHS R01 CA202778NEI NIH HHS R01 EY025342NEI NIH HHS R43 EY022516NHLBI NIH HHS R01 HL077671NHLBI NIH HHS R01 HL084516NHLBI NIH HHS T32 HL007576NHLBI NIH HHS U54 HL112311NIAMS NIH HHS R01 AR064788NIAMS NIH HHS R43 AR063509NINDS NIH HHS R01 NS080893NINDS NIH HHS U01 NS083573
Abstract
Activating mutations in Gαq proteins, which form the α subunit of certain heterotrimeric G proteins, drive uveal melanoma oncogenesis by triggering multiple downstream signaling pathways, including PLC/PKC, Rho/Rac, and YAP. Here we show that the small GTPase ARF6 acts as a proximal node of oncogenic Gαq signaling to induce all of these downstream pathways as well as β-catenin signaling. ARF6 activates these diverse pathways through a common mechanism: the trafficking of GNAQ and β-catenin from the plasma membrane to cytoplasmic vesicles and the nucleus, respectively. Blocking ARF6 with a small-molecule inhibitor reduces uveal melanoma cell proliferation and tumorigenesis in a mouse model, confirming the functional relevance of this pathway and suggesting a therapeutic strategy for Gα-mediated diseases.
Indexed as
ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsbeta CateninCell Line, TumorCell MembraneCell NucleusCell ProliferationCytoplasmGTP-Binding Protein alpha Subunits, Gq-G11HumansMelanomaMiceNeoplasm TransplantationProtein TransportSignal TransductionADP-Ribosylation Factor 6ADP-Ribosylation FactorsARF6 protein, humanArf6 protein, mousebeta CateninGNAQ protein, humanGTP-Binding Protein alpha Subunits, Gq-G11Small Molecule Libraries
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