Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression.

ABSTRACT: Due to the enhanced glycolytic rate, cancer cells generate lactate copiously, subsequently promoting the lactylation of histones. While previous studies have explored the impact of histone lactylation in modulating gene expression, the precise role of this epigenetic modification in regulating oncogenes is largely unchartered. In this study, using breast cancer cell lines and their mutants exhibiting lactate-deficient metabolome, we have identified that an enhanced rate of aerobic glycolysis supports c-Myc expression via promoter-level histone lactylation. Interestingly, c-Myc further transcriptionally upregulates serine/arginine splicing factor 10 (SRSF10) to drive alternative splicing of MDM4 and Bcl-x in breast cancer cells. Moreover, our results reveal that restricting the activity of

SUBMITTER: Pandkar MR 

PROVIDER: S-EPMC10425713 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature