Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.

ABSTRACT: Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells. Androgens reprogram mTOR-chromatin associations in an AR-dependent manner in which activation of mTOR-dependent metabolic gene networks is essential for androgen-induced aerobic glycolysis and mitoch

SUBMITTER: Audet-Walsh E 

PROVIDER: S-EPMC5558925 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature