The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1.
Altogether, these data define an AR/mTOR nuclear axis, in the context of prostate cancer, as a novel pathway regulating SREBF1 activity and citrate metabolism.<b>Implications:</b> The finding that an AR/mTOR complex promotes SREBF1 expression and activity enhances our understanding of the metabolic adaptation necessary for prostate cancer cell growth and suggests novel therapeutic approaches to target metabolic vulnerabilities in tumors.<i></i>.
Overactivation of SREBP1 and elevated lipid biogenesis are considered the major characteristics in malignancies of prostate cancer, endometrial cancer, and glioblastoma.
Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells.
Nelfinavir inhibited androgen receptor activation in androgen-sensitive prostate cancer and the nuclear translocation of the fusion proteins sterol regulatory element binding protein-1 (SREBP-1)-enhanced green fluorescence protein (EGFP) and activating transcription factor 6 (ATF6)-EGFP in castration-resistant prostate cancer cells, viewed under confocal microscopy.
In the present study, we showed that KLF5 acts as a key regulator controlling the expression of FASN (fatty acid synthase) through an interaction with SREBP-1 (sterol-regulatory-element-binding protein-1) in the androgen-dependent LNCaP prostate cancer cell line.
In clinical prostate cancer specimens from patients with varying grades of disease, the stained tissue sections showed high levels of SREBP-1 protein compared with noncancerous prostate tissue.