Prostate lineage-specific metabolism governs luminal differentiation and response to antiandrogen treatment.

ABSTRACT: Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes are well known to drive prostate lineage transitions, it remains unclear how upstream metabolic signalling contributes to the regulation of prostate epithelial identity. To fill this gap, we developed an approach to perform metabolomics on primary prostate epithelial cells. Using this approach, we discovered that the basal and luminal cells of the prostate exhibit distinct metabolomes and nutrient utilization patterns. Furthermore, basal-to-luminal differentiation is accompanied by increased pyruvate oxidation. We establish the mitochondrial pyruvate carrier and subsequent lactate accumulation as regulators of prostate luminal identity. Inhibition of the mito

SUBMITTER: Giafaglione JM 

PROVIDER: S-EPMC10709144 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature