Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer progression [ChIP-seq]

Whether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression. We performed ChIP-seq of mTOR to study its role in LNCaP cells with or without androgen stimulation. The study was done twice independently; processed data are shown as a pool of either vehicle-treated samples or R1881-treated samples. Overall design: Cells were seeded in media deprived from steroids. 48h later, cell were treated with 10nM R1881 or vehicle (EtOH) for 48h before crosslink and ChIP.