Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma.

ABSTRACT:

Purpose

Metastatic uveal melanoma (UM) has a very poor prognosis and no effective therapy. Despite remarkable advances in treatment of cutaneous melanoma, UM remains recalcitrant to chemotherapy, small-molecule kinase inhibitors, and immune-based therapy.

Methods

We assessed two sets of oxidative phosphorylation (OxPhos) genes within 9858 tumors across 31 cancer types. An OxPhos inhibitor was used to characterize differential metabolic programming of highly metastatic monosomy 3 (M3) UM. Seahorse analysis and global metabolomics profiling were done to identify metabolic vulnerabilities. Analyses of UM TCGA data set were performed to determine expressions of key OxPhos effectors in M3 and non-M3 UM. We used targeted knockdown of succinate dehydrogenase A (SDHA) to determine t

SUBMITTER: Chattopadhyay C 

PROVIDER: S-EPMC6785781 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature