Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy

Shi, Yan; Han, Jing; Tennakoon, Jayantha B.; Mehta, Fabiola F.; Merchant, Fatima A.; Burns, Alan R.; Howe, Matthew K.; McDonnell, Donald P.; Frigo, Daniel E.

doi:10.1210/me.2012-1260

Cited by 80 publications

(96 citation statements)

References 86 publications

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“…The androgen-signaling pathway has been shown to regulate several metabolic pathways including both aerobic glycolysis and mitochondrial respiration (4,6,34). Accordingly, following sustained treatment of the synthetic androgen R1881, we observed an increase of about 400% in glucose uptake (Fig.…”

Section: Androgens Reprogram Pca Cell Metabolismmentioning

confidence: 72%

Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer

et al. 2017

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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.

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Section: Androgens Reprogram Pca Cell Metabolismmentioning

confidence: 72%

Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer

et al. 2017

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“…In fact, it has been suggested that androgens assert their proliferative role by activating the autophagy pathway (Shi et al 2013). Analysis of AR expression by IHC demonstrated a significant difference between the Atg7 +/+ and Atg7 Δ/Δ tumor tissues beyond 3 mo after TAM.…”

Section: G12dmentioning

confidence: 99%

Atg7 cooperates with Pten loss to drive prostate cancer tumor growth

et al. 2016

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Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer.

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“…The role of autophagy in cancer therapy is complex [17,26] . To investigate the role of autophagy induced by PD, BEL-7402 cells were pretreated with CQ or BAF for 1 h before PD treatment.…”

Section: Inhibition Of Autophagy Enhances Pd-induced Proliferation Inmentioning

confidence: 99%

Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells

Tang

et al. 2015

Acta Pharmacol Sin

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Aim: Platycodin D, the main saponin isolated from Chinese herb Platycodonis Radix, exhibits anticancer activities against various cancer cell lines. Here we evaluated its anticancer action against human hepatocellular carcinoma cells in vitro and in vivo, and elucidated the relationship between platycodin D-induced apoptosis and autophagy. Methods: The viability of human hepatocellular carcinoma BEL-7402 cells was evaluated with MTT assay, and the apoptosis was examined using Annexin V/PI and Hoechst 33342 staining assays. Monodansylcadaverine (MDC) staining was used to label autophagic vacuoles. The proteins were detected using Western blot analysis. For studying its anticancer action in vivo, platycodin D (5 and 10 mg·kg -1 ·d -1 ) was intraperitoneally injected to BEL-7402-bearing mice for 21 days.

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Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy

Cited by 80 publications

References 86 publications

Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer

Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer

Atg7 cooperates with Pten loss to drive prostate cancer tumor growth

Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells

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