ArticleScience signaling2015
Cell type-specific abundance of 4EBP1 primes prostate cancer sensitivity or resistance to PI3K pathway inhibitors.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
29 citing papers in PubMed, 44 citations in OpenAlex.
- A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.Investigational new drugs · 2018Trial
- Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer.European journal of cancer (Oxford, England : 1990) · 2017Trial
- 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
- Multi-omics integration constructs a senescence-based prognostic model and identifies EIF4EBP1 as a therapeutic target in clear cell renal cell carcinoma.Discover oncology · 2026Article
- Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer.Science advances · 2025Article
- Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer.Cancer discovery · 2023Article
- High expression of autophagy-related geneWorld journal of clinical cases · 2023Article
- Multi-omic profiling reveals an RNA processing rheostat that predisposes to prostate cancer.EMBO molecular medicine · 2023Article
- Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases.Science translational medicine · 2023Article
- The long non-coding RNA PVT1 promotes tumorigenesis of cutaneous squamous cell carcinoma via interaction with 4EBP1.Cell death discovery · 2023Article
- Regulation of eIF4E guides a unique translational program to control erythroid maturation.Science advances · 2022Article
- Defining cellular population dynamics at single-cell resolution during prostate cancer progression.eLife · 2022Article
- Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation.NAR cancer · 2022Article
- Dual contribution of the mTOR pathway and of the metabolism of amino acids in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Cancer Plasticity: The Role of mRNA Translation.Trends in cancer · 2021Review
- ZebrafishVaccines · 2020Article
- The androgen receptor regulates a druggable translational regulon in advanced prostate cancer.Science translational medicine · 2019Article
- Identification of biomarker microRNA-mRNA regulatory pairs for predicting the docetaxel resistance in prostate cancer.Journal of Cancer · 2019Article
- The Secret Life of Translation Initiation in Prostate Cancer.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Pharmacological inhibitors against the PI3K-AKT-mTOR (phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin) pathway, a frequently deregulated signaling pathway in cancer, are clinically promising, but the development of drug resistance is a major limitation. We found that 4EBP1, the central inhibitor of cap-dependent translation, was a critical regulator of both prostate cancer initiation and maintenance downstream of mTOR signaling in a genetic mouse model. 4EBP1 abundance was distinctly different between the epithelial cell types of the normal prostate. Of tumor-prone prostate epithelial cell types, luminal epithelial cells exhibited the highest transcript and protein abundance of 4EBP1 and the lowest protein synthesis rates, which mediated resistance to both pharmacologic and genetic inhibition of the PI3K-AKT-mTOR signaling pathway. Decreasing total 4EBP1 abundance reversed resistance in drug-insensitive cells. Increased 4EBP1 abundance was a common feature in prostate cancer patients who had been treated with the PI3K pathway inhibitor BKM120; thus, 4EBP1 may be associated with drug resistance in human tumors. Our findings reveal a molecular program controlling cell type-specific 4EBP1 abundance coupled to the regulation of global protein synthesis rates that renders each epithelial cell type of the prostate uniquely sensitive or resistant to inhibitors of the PI3K-AKT-mTOR signaling pathway.
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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.