ArticleThe Journal of biological chemistry2012
Androgen Receptor Enhances p27 Degradation in Prostate Cancer Cells through Rapid and Selective TORC2 Activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Castration-resistant prostate cancer cells are addicted to the high activity of cyclin-dependent kinase 2.Molecular oncology · 2026Article
- ARv7 promotes the escape of prostate cancer cells from androgen deprivation therapy-induced senescence by mediating the SKP2/p27 axis.BMC biology · 2025Article
- Review
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Combination with Ralaniten Analogs for the Treatment of Androgen Receptor-positive Prostate and Breast Cancers.Molecular cancer therapeutics · 2022Article
- Mechanisms of abemaciclib, a CDK4/6 inhibitor, induced apoptotic cell death in prostate cancer cells in vitro.Translational oncology · 2022Article
- Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer.International journal of molecular sciences · 2021Review
- MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT.The Journal of clinical investigation · 2021Article
- Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents.Frontiers in pharmacology · 2021Review
- Gender Differences in Gastric Cancer Survival: 99,922 Cases Based on the SEER Database.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2020Article
- The Enigmatic Role of Serum & Glucocorticoid Inducible Kinase 1 in the Endometrium.Frontiers in cell and developmental biology · 2020Review
- Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer.OncoTargets and therapy · 2020Review
- Review
- Review
- Article
- Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling.Oncogene · 2017Article
- A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth.SLAS discovery : advancing life sciences R & D · 2017Article
- mTORC2 regulates multiple aspects of NKT-cell development and function.European journal of immunology · 2017Article
- Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development.Journal of hematology & oncology · 2016Article
- Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors.Nuclear receptor signaling · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Androgen receptor (AR) plays a central role in prostate cancer (PCa) growth, with androgen deprivation or AR down-regulation causing cell-cycle arrest and accumulation of the p27 cyclin-dependent kinase inhibitor. The molecular basis for this AR regulation of cell-cycle progression remains unclear. Here we demonstrate that androgen can rapidly reduce p27 protein in PCa cells by increasing its proteasome-mediated degradation. This rapid androgen-stimulated p27 degradation was mediated by AKT through the phosphorylation of p27 T157. Significantly, androgen increased TORC2-mediated AKT S473 phosphorylation without affecting the PDK1-mediated AKT T308 phosphorylation or TORC1 activity. The TORC2 activation was further supported by enhanced mTOR/RICTOR association and increased phosphorylation of additional TORC2 substrates, SGK1 and PKCα. The androgen-stimulated nuclear translocation of AR was associated with markedly-increased nuclear SIN1, a critical component of TORC2. Finally, the androgen-mediated TORC2/AKT activation targets a subset of AKT substrates including p27 and FOXO1, but not PRAS40. This study reveals a pathway linking AR to a selective activation of TORC2, the subsequent activation of AKT, and phosphorylation of a discrete set of AKT substrates that regulate cellular proliferation and survival. These findings establish that TORC2 can function as a central regulator of growth in response to signals that are distinct from those regulating TORC1, and support efforts to target TORC2 for cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.