کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107808 | 1083702 | 2014 | 15 صفحه PDF | دانلود رایگان |
• The GNAQ oncogene stimulates the transcriptional coactivator YAP in uveal melanoma
• A Hippo- and PLCβ-independent Rho GTPase signaling circuitry links GNAQ to YAP
• YAP is essential for GNAQ-induced uveal melanoma cell proliferation
• YAP represents a suitable therapeutic target for melanomas harboring GNAQ mutations
SummaryMutually 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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Journal: - Volume 25, Issue 6, 16 June 2014, Pages 831–845