BAP1 Loss Affords Lipotoxicity Resistance in Uveal Melanoma.

ABSTRACT: Uveal melanoma (UM) is an aggressive intraocular malignancy. Despite effective control of primary tumors, ~50% of UM patients develop metastases, with the liver being the predominant secondary site. BAP1 deficiency, present in ~80% of metastatic UM cases, is strongly associated with increased metastatic risk and poor prognosis. In silico analysis of UM patient samples suggests that reduced BAP1 is linked to enhanced expression of genes involved in fatty acid processing; therefore, we hypothesize that BAP1 deficiency primes UM cells for survival in the hepatic microenvironment by enhancing lipid tolerance and oxidative stress responses. Our findings demonstrate BAP1-mutant UM resist lipotoxicity, whereas BAP1-competent UM exhibit sensitivity due to lipid peroxide accumulation-a hallmark of

SUBMITTER: Cunanan CJ 

PROVIDER: S-EPMC12040534 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature