ArticleCell cycle (Georgetown, Tex.)2011
High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1.
Article in Cell cycle (Georgetown, Tex.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 115 citations in OpenAlex.
- Discovery of indole- and quinolone-based inhibitors of the mTOR/Akt/Pi3K pathway for the potential treatment of autism and certain types of cancer.RSC medicinal chemistry · 2026Article
- The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells.Cancers · 2025Article
- Article
- Factors that determine cell fate in mitotically arrested cancer cells.Frontiers in cell and developmental biology · 2025Article
- Tumor Necrosis Factor Receptor-2 Signals Clear-Cell Renal Carcinoma Proliferation via Phosphorylated 4E Binding Protein-1 and Mitochondrial Gene Translation.The American journal of pathology · 2024Article
- Signalling pathway crosstalk stimulated by L-proline drives mouse embryonic stem cells to primitive-ectoderm-like cells.Development (Cambridge, England) · 2023Article
- Formulation of cost-effective medium and optimization studies for enhanced production of rapamycin.Microbial cell factories · 2023Article
- A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress.Cell death & disease · 2023Article
- Review
- AR and PI3K/AKT in Prostate Cancer: A Tale of Two Interconnected Pathways.International journal of molecular sciences · 2023Review
- Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues.Frontiers in bioengineering and biotechnology · 2023Article
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- An amino acid-defined diet impairs tumour growth in mice by promoting endoplasmic reticulum stress and mTOR inhibition.Molecular metabolism · 2022Article
- Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways.Frontiers in oncology · 2022Article
- Modulation of mTOR signaling by radiation and rapamycin treatment in canine mast cell cancer cells.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2022Article
- Cancer cells with defective RB and CDKN2A are resistant to the apoptotic effects of rapamycin.Cancer letters · 2021Article
- The Secrets of Alternative Autophagy.Cells · 2021Review
- Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.BMC cancer · 2021Article
- Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-HER2 therapy in PIK3CA-mutant HER2-positive breast cancer cells.Scientific reports · 2020Article
- Development of ErbB2-Targeting Liposomes for Enhancing Drug Delivery to ErbB2-Positive Breast Cancer.Pharmaceutics · 2020Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
mTOR, the mammalian target of rapamycin, has been widely implicated in signals that promote cell cycle progression and survival in cancer cells. Rapamycin, which inhibits mTOR with high specificity, has consequently attracted much attention as an anti-cancer therapeutic. Rapamycin suppresses phosphorylation of S6 kinase at nano-molar concentrations, however at higher micro-molar doses, rapamycin induces apoptosis in several human cancer cell lines. While much is known about the effect of low dose rapamycin treatment, the mechanistic basis for the apoptotic effects of high-dose rapamycin treatment is not understood. We report here that the apoptotic effects of high-dose rapamycin treatment correlate with suppressing phosphorylation of the mTOR complex 1 substrate, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4E-BP1). Consistent with this observation, ablation of eIF4E also resulted in apoptorsis in MDA-MB 231 breast cancer cells. We also provide evidence that the differential dose effects of rapamycin are correlated with partial and complete dissociation of Raptor from mTORC1 at low and high doses, respectively. In contrast with MDA-MB-231 cells, MCF-7 breast cancer cells survived rapamycin-induced suppression of 4E-BP1 phosphorylation. We show that survival correlated with a hyper-phosphorylation of Akt at S473 at high rapamycin doses, the suppression of which conferred rapamycin sensitivity. This study reveals that the apoptotic effect of rapamycin requires doses that completely dissociate Raptor from mTORC1 and suppress that phosphorylation of 4E-BP1 and inhibit eIF4E.
Indexed as
Identifiers
What OpenQuestion holds
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.