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Abstract: xclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gaq family members, have been identified in ~ 83% and ~ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gaq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cß and the canonical Hippo pathway. Furthermore, we show that Gaq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy.
Fuente: Cancer Cell, 2014, 16, 25(6), 831-45
Editorial: Cell Press
Fecha de publicación: 16/06/2014
Nº de páginas: 29
Tipo de publicación: Artículo de Revista
DOI: 10.1016/j.ccr.2014.04.016.
ISSN: 1535-6108,1878-3686
Leer publicación
FENG, XIAODONG
DEGESE, MARIA SOL
IGLESIAS BARTOLOME, RAMIRO
JOSE PEDRO VAQUE DIEZ
MOLINOLO, ALFREDO A.
RODRIGUES, MURILO
ZAIDI, M. RAZA
KSANDER, BRUCE R.
MERLINO, GLENN
SODHI, AKRIT
CHEN, QIANMING
GUTKIND, SILVIO
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