Metabolic fitness of NAC1-deficient Tregs in the tumor microenvironment fuels tumor growth.

ABSTRACT: The nucleus accumbens-associated protein 1 (NAC1) has recently emerged as a pivotal factor in oncogenesis by promoting glycolysis. Deletion of NAC1 in regulatory T cells (Tregs) has been shown to enhance FoxP3 stability, a suppressor of glycolysis. This study delves into the intriguing dual role of NAC1, uncovering that Treg-specific deletion of NAC1 fosters metabolic fitness in Tregs, thereby promoting tumorigenesis. Our results unveil that NAC1-deficient Tregs exhibited prolonged survival and heightened function, particularly in acidic environments. Mechanistically, we find that NAC1-deficient Tregs adapted to adverse conditions by upregulating FoxP3 expression, engaging in CD36-mediated lipid metabolism, and enhancing peroxisome proliferator-activated receptor gamma coactivator 1-alpha-

SUBMITTER: Kumar A 

PROVIDER: S-EPMC11949012 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature