| First Author | Feng X | Year | 2014 |
| Journal | Cancer Cell | Volume | 25 |
| Issue | 6 | Pages | 831-45 |
| PubMed ID | 24882515 | Mgi Jnum | J:213498 |
| Mgi Id | MGI:5585205 | Doi | 10.1016/j.ccr.2014.04.016 |
| Citation | Feng X, et al. (2014) Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 25(6):831-45 |
| abstractText | Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Galphaq family members, have been identified in approximately 83% and approximately 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 Galphaq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cbeta and the canonical Hippo pathway. Furthermore, we show that Galphaq 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. |
