journal contribution
posted on 2023-03-31, 00:45 authored by Étienne Audet-Walsh, Tracey Yee, Shawn McGuirk, Mathieu Vernier, Carlo Ouellet, Julie St-Pierre, Vincent Giguère The files contains extended Materials and Methods, Supplementary Table 1 and 2 contains primer sequences, Supplementary Table 3 contains Cox Regression Analysis, Figure S1 presents ChIP-sequencing data, Figure S2 show regulation of expression of ERRg by the androgen receptor, Figure S3 shows ERRg control of metabolic gene expression, Figure S4 and S5 ERRg control of prostate cancer cell metabolism, Figure S6 shows ERRa expression in relation to prostate cancer recurrence.
Funding
Terry Fox Research Institute
Canadian Institutes of Health Research
History
ARTICLE ABSTRACT
How androgen signaling contributes to the oncometabolic state of prostate cancer remains unclear. Here, we show how the estrogen-related receptor γ (ERRγ) negatively controls mitochondrial respiration in prostate cancer cells. Sustained treatment of prostate cancer cells with androgens increased the activity of several metabolic pathways, including aerobic glycolysis, mitochondrial respiration, and lipid synthesis. An analysis of the intersection of gene expression, binding events, and motif analyses after androgen exposure identified a metabolic gene expression signature associated with the action of ERRγ. This metabolic state paralleled the loss of ERRγ expression. It occurred in both androgen-dependent and castration-resistant prostate cancer and was associated with cell proliferation. Clinically, we observed an inverse relationship between ERRγ expression and disease severity. These results illuminate a mechanism in which androgen-dependent repression of ERRγ reprograms prostate cancer cell metabolism to favor mitochondrial activity and cell proliferation. Furthermore, they rationalize strategies to reactivate ERRγ signaling as a generalized therapeutic approach to manage prostate cancer. Cancer Res; 77(2); 378–89. ©2016 AACR.
