Targeting ErbB3 and Cellular NADPH/NADP⁺ Abundance Sensitizes Cutaneous Melanomas to Ferroptosis Inducers.

ABSTRACT: Melanoma is a serious health challenge. Ferroptosis is a regulated form of oxidative cell death that shows varied efficacy in melanoma. We aimed to better understand the molecular basis for this differential ferroptosis sensitivity. We find that elevated expression of ErbB3 (V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homologue 3) associates with ferroptosis resistance and that ErbB3 knockdown sensitizes to ferroptosis inducers. ErbB3 depletion also promotes a marked reduction in the cellular ratio of GSH/GSSG (reduced/oxidized glutathione) and that of NADPH/NADP⁺ (reduced/oxidized nicotinamide adenine dinucleotide phosphate), together with an increase in the abundance of the lipid peroxidation product malondialdehyde (MDA). We identify several small molecule inhibitor

SUBMITTER: Leu JI 

PROVIDER: S-EPMC9208338 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature