| First Author | Audet-Walsh É | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 2 | Pages | 378-389 |
| PubMed ID | 27821488 | Mgi Jnum | J:238489 |
| Mgi Id | MGI:5822937 | Doi | 10.1158/0008-5472.CAN-16-1204 |
| Citation | Audet-Walsh E, et al. (2017) Androgen-Dependent Repression of ERRgamma Reprograms Metabolism in Prostate Cancer. Cancer Res 77(2):378-389 |
| abstractText | How androgen signaling contributes to the oncometabolic state of prostate cancer remains unclear. Here, we show how the estrogen-related receptor gamma (ERRgamma) 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 ERRgamma. This metabolic state paralleled the loss of ERRgamma 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 ERRgamma expression and disease severity. These results illuminate a mechanism in which androgen-dependent repression of ERRgamma reprograms prostate cancer cell metabolism to favor mitochondrial activity and cell proliferation. Furthermore, they rationalize strategies to reactivate ERRgamma signaling as a generalized therapeutic approach to manage prostate cancer. Cancer Res; 77(2); 378-89. (c)2016 AACR. |
