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Ref Type Journal Article
PMID (27265506)
Authors Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, Rogers A, Zhu W, Richards JR, Winter JM, Zhu J, Dunn C, Bajji A, Shenderovich M, Mueller AL, Woodman SE, Harbour JW, Thomas KR, Odelberg SJ, Ostanin K, Li DY
Title ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 29 6 2016 06 13 889-904 Cancer Cell
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
NAV-2729 NAV-2729 binds to and inhibits ARF6, which may result in decreased tumor growth (PMID: 27265506).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References