Cell reportsDec 5, 2019

Activation of YAP/TAZ Proteins May Trigger and Promote Uveal Melanoma

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

Genetic activation of YAP is sufficient to initiate uveal melanoma (UM) in a mouse model.

Lats1/2 kinases are shown to suppress UM formation specifically in uveal melanocytes.
YAP/TAZ activation due to Lats1/2 deletion cooperates with Kras to enhance UM progression.
Inhibition of both YAP/TAZ and Ras/MAPK pathways may synergize to reduce the growth of human UM cells.
The findings underscore the role of Lats-YAP/TAZ signaling in UM initiation and progression in vivo.

Simplified

Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations. Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GαQ/11)-mediated transformation, although whether and how they contribute to UM genesis in vivo remain unclear. Here, we adapt an adeno-associated virus (AAV)-based ocular injection method to directly deliver Cre recombinase into the mouse uveal tract and demonstrate that Lats1/2 kinases suppress UM formation specifically in uveal melanocytes. We find that genetic activation of YAP, but not Kras, is sufficient to initiate UM. We show that YAP/TAZ activation induced by Lats1/2 deletion cooperates with Kras to promote UM progression via downstream transcriptional reinforcement. Furthermore, dual inhibition of YAP/TAZ and Ras/MAPK synergizes to suppress oncogenic growth of human UM cells. Our data highlight the functional significance of Lats-YAP/TAZ in UM initiation and progression in vivo and suggest combination inhibition of YAP/TAZ and Ras/MAPK as a new therapeutic strategy for UM.

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Activation of YAP/TAZ Proteins May Trigger and Promote Uveal Melanoma

Abstract

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