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Updated: Mar 20, 2026

Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
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ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma

Jae Hyuk Yoo1, Dallas S Shi2, Allie H Grossmann3

  • 1Department 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.

Cancer Cell
|June 7, 2016
PubMed

Insights

Activating mutations in Gαq proteins drive uveal melanoma. The small GTPase ARF6 acts as a key signaling node, controlling oncogenic pathways and tumor growth, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Activating mutations in Gαq proteins are key drivers of uveal melanoma.
  • Gαq signaling activates multiple downstream pathways, including PLC/PKC, Rho/Rac, and YAP, promoting oncogenesis.

Purpose of the Study:

  • To investigate the role of the small GTPase ARF6 in oncogenic Gαq signaling in uveal melanoma.
  • To elucidate the mechanism by which ARF6 mediates Gαq-driven downstream pathways.

Main Methods:

  • Utilized cell culture models of uveal melanoma.
  • Employed small-molecule inhibitors to block ARF6 activity.
  • Investigated protein trafficking and signaling pathway activation.
  • Assessed tumor proliferation and tumorigenesis in a mouse model.

Main Results:

  • ARF6 acts as a proximal node in oncogenic Gαq signaling, inducing PLC/PKC, Rho/Rac, YAP, and β-catenin pathways.
  • ARF6 mediates pathway activation through the trafficking of GNAQ and β-catenin.
  • Inhibition of ARF6 reduced uveal melanoma cell proliferation and tumorigenesis in vivo.

Conclusions:

  • ARF6 is a critical mediator of Gαq-driven uveal melanoma.
  • Targeting ARF6 represents a potential therapeutic strategy for Gαq-mediated diseases.
  • Understanding ARF6's role in protein trafficking provides insights into melanoma oncogenesis.

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