ArticleGenes & development2017
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Article in Genes & development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 143 citations in OpenAlex.
- Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.Nature chemical biology · 2026Article
- Testosterone and cancers: biological functions, molecular mechanisms and therapy.Molecular cancer · 2026Review
- Intermittent Fasting and Androgen Receptor Signaling in Prostate Cancer: Metabolic Crosstalk and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Identification and validation of critical mitochondrial hub genes for prostate cancer.Oncology letters · 2026Article
- The mTOR signaling pathway regulates key steps of mammary gland organoid genesis in a temporal manner.Scientific reports · 2026Article
- Mitochondrial convergence of ferroptosis and cuproptosis in castration-resistant prostate cancer: From metabolic vulnerabilities to therapeutic targeting.BBA advances · 2026Review
- Beyond molecular classification: integrating signaling, subcellular, and immune reprogramming in endometrial cancer.Frontiers in oncology · 2026Review
- Deep Sequencing Reveals Novel Mutations inInternational journal of molecular sciences · 2025Article
- Conformation-specific synthetic intrabodies modulate mTOR signaling with subcellular spatial resolution.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Relationship between androgen receptor and androgen receptor-related protein expression in breast cancers focusing on morphologically identified carcinoma with apocrine differentiation.Scientific reports · 2025Article
- Impact of Endocrine Disruptors on the Genitourinary Tract.Journal of xenobiotics · 2024Review
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Low protein diet protects the liver from Salmonella Typhimurium-mediated injury by modulating the mTOR/autophagy axis in macrophages.Communications biology · 2024Article
- Review
- Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells.Nature communications · 2024Article
- Elevated LAMTOR4 Expression Is Associated with Lethal Prostate Cancer and Its Knockdown Decreases Cell Proliferation, Invasion, and Migration In Vitro.International journal of molecular sciences · 2024Article
- Nuclear mTOR Signaling Orchestrates Transcriptional Programs Underlying Cellular Growth and Metabolism.Cells · 2024Review
- Article
- Mitochondrial Proteins as Metabolic Biomarkers and Sites for Therapeutic Intervention in Primary and Metastatic Cancers.Mini reviews in medicinal chemistry · 2024Review
- Mesenchymal stem cells lose the senescent phenotype under 3D cultivation.Stem cell research & therapy · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells. Androgens reprogram mTOR-chromatin associations in an AR-dependent manner in which activation of mTOR-dependent metabolic gene networks is essential for androgen-induced aerobic glycolysis and mitochondrial respiration. In models of castration-resistant PCa cells, mTOR was capable of transcriptionally regulating metabolic gene programs in the absence of androgens, highlighting a potential novel castration resistance mechanism to sustain cell metabolism even without a functional AR. Remarkably, we demonstrate that increased mTOR nuclear localization is indicative of poor prognosis in patients, with the highest levels detected in castration-resistant PCa tumors and metastases. Identification of a functional mTOR targeted multigene signature robustly discriminates between normal prostate tissues, primary tumors, and hormone refractory metastatic samples but is also predictive of cancer recurrence. This study thus underscores a paradigm shift from AR to nuclear mTOR as being the master transcriptional regulator of metabolism in PCa.
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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.