ArticleScience translational medicine2019
The androgen receptor regulates a druggable translational regulon in advanced prostate cancer.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 73 citations in OpenAlex.
- A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.bioRxiv : the preprint server for biology · 2026Article
- SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Therapeutic targeting of the eIF4E cap-binding domain reveals control of lineage fate in prostate cancer.The Journal of clinical investigation · 2026Article
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic target.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Evolving roles for the androgen receptor and its protein interactome in castration-resistant prostate cancer.Oncogene · 2025Review
- Article
- The EIF4EBP1 gene encoding 4EBP1 is transcriptionally upregulated by MYC and linked to shorter survival in medulloblastoma.Cell death discovery · 2025Article
- Small-molecule RNA therapeutics to target prostate cancer.Cancer cell · 2025Article
- NXP800 Activates the Unfolded Protein Response, Altering AR and E2F Function to Impact Castration-Resistant Prostate Cancer Growth.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The impact of androgen-induced translation in modulating androgen receptor activity.Biology direct · 2024Article
- Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.Science advances · 2024Article
- Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation.Nature communications · 2024Article
- Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer.Cancer discovery · 2023Article
- WTAP boosts lipid oxidation and induces diabetic cardiac fibrosis by enhancing AR methylation.iScience · 2023Article
- AR activates YAP/TAZ differentially in prostate cancer.Life science alliance · 2023Article
- The transcription factor DUX4 orchestrates translational reprogramming by broadly suppressing translation efficiency and promoting expression of DUX4-induced mRNAs.PLoS biology · 2023Article
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24 authors at 3 institutions in 1 country.
Funding
Abstract
The androgen receptor (AR) is a driver of cellular differentiation and prostate cancer development. An extensive body of work has linked these normal and aberrant cellular processes to mRNA transcription; however, the extent to which AR regulates posttranscriptional gene regulation remains unknown. Here, we demonstrate that AR uses the translation machinery to shape the cellular proteome. We show that AR is a negative regulator of protein synthesis and identify an unexpected relationship between AR and the process of translation initiation in vivo. This is mediated through direct transcriptional control of the translation inhibitor 4EBP1. We demonstrate that lowering AR abundance increases the assembly of the eIF4F translation initiation complex, which drives enhanced tumor cell proliferation. Furthermore, we uncover a network of pro-proliferation mRNAs characterized by a guanine-rich cis-regulatory element that is particularly sensitive to eIF4F hyperactivity. Using both genetic and pharmacologic methods, we demonstrate that dissociation of the eIF4F complex reverses the proliferation program, resulting in decreased tumor growth and improved survival in preclinical models. Our findings reveal a druggable nexus that functionally links the processes of mRNA transcription and translation initiation in an emerging class of lethal AR-deficient prostate cancer.
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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.