Whole-genome CRISPR screening identifies PI3K/AKT as a downstream component of the oncogenic GNAQ-focal adhesion kinase signaling circuitry.

ABSTRACT: G proteins and G protein-coupled receptors activate a diverse array of signal transduction pathways that promote cell growth and survival. Indeed, hot spot-activating mutations in GNAQ/GNA11, encoding Gαq proteins, are known to be driver oncogenes in uveal melanoma (UM), for which there are limited effective therapies currently available. Focal adhesion kinase (FAK) has been recently shown to be a central mediator of Gαq-driven signaling in UM, and as a result, is being explored clinically as a therapeutic target for UM, both alone and in combination therapies. Despite this, the repertoire of Gαq/FAK-regulated signaling mechanisms have not been fully elucidated. Here, we used a whole-genome CRISPR screen in GNAQ-mutant UM cells to identify mechanisms that, when overactivated, lead to reduc

SUBMITTER: Arang N 

PROVIDER: S-EPMC9922814 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature