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Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

ABSTRACT: Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric G?q 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 G?q stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase C? and the canonical Hippo pathway. Furthermore, we show that G?q 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.

SUBMITTER: Feng X 

PROVIDER: S-EPMC4074519 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

Feng Xiaodong X   Degese Maria Sol MS   Iglesias-Bartolome Ramiro R   Vaque Jose P JP   Molinolo Alfredo A AA   Rodrigues Murilo M   Zaidi M Raza MR   Ksander Bruce R BR   Merlino Glenn G   Sodhi Akrit A   Chen Qianming Q   Gutkind J Silvio JS  

Cancer cell 20140529 6

Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq 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  ...[more]

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