MITF deficiency and oncogenic GNAQ each promote proliferation programs in zebrafish melanocyte lineage cells.

ABSTRACT: Uveal melanoma (UM) is the most common primary malignancy of the adult eye but lacks any FDA-approved therapy for the deadly metastatic disease. Thus, there is a great need to dissect the driving mechanisms for UM and develop strategies to evaluate potential therapeutics. Using an autochthonous zebrafish model, we previously identified MITF, the master melanocyte transcription factor, as a tumor suppressor in GNAQ^Q209L -driven UM. Here, we show that zebrafish mitfa-deficient GNAQ^Q209L -driven tumors significantly up-regulate neural crest markers, and that higher expression of a melanoma-associated neural crest signature correlates with poor UM patient survival. We further determined how the mitfa-null state, as well as expression of GNAQ^Q209L , YAP^S127

SUBMITTER: Phelps GB 

PROVIDER: S-EPMC9541221 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature