ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma.
Cancer Cell
; 29(6): 889-904, 2016 06 13.
Article
em En
| MEDLINE
| ID: mdl-27265506
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 ß-catenin signaling. ARF6 activates these diverse pathways through a common mechanism the trafficking of GNAQ and ß-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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Uveais
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Fatores de Ribosilação do ADP
/
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
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Beta Catenina
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Bibliotecas de Moléculas Pequenas
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Melanoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos