[HTML][HTML] Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry
X Feng, MS Degese, R Iglesias-Bartolome, JP Vaque… - Cancer cell, 2014 - cell.com
Cancer cell, 2014•cell.com
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 that Gαq stimulates YAP …
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 that Gαq stimulates YAP …
Summary
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 that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq 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.
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