Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein.

ABSTRACT: Immunotherapy using checkpoint blockers (antibodies) has been a major advance in recent years in the management of various types of solid cancers including lung cancer. One target of checkpoint blockers is programmed death ligand 1 (PD-L1) expressed by cancer cells, which engages programmed death 1 on T cells and Natural Killer (NK) cells resulting in suppression of their activation and cancer-killing function, respectively. Apart from antibodies, other clinically relevant agents that can inhibit PD-L1 are limited. PD-L1 protein stability depends on its glycosylation. Here we show that l-glutamine:d-fructose-6-phosphate amidotransferase 1 (GFAT1), a rate-limiting enzyme of the hexosamine biosynthesis pathway, which produces uridine diphosphate-N-acetyl-β-glucosamine, a precursor for glycos

SUBMITTER: Chen W 

PROVIDER: S-EPMC8491135 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature