ArticleHaematologica2017
Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas.
Article in Haematologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Sweet apple e-cigarette vapor differentially modulates the mTOR pathway in oral squamous cell carcinoma cell lines.Frontiers in oncology · 2026Article
- Development of a cancer metastasis-associated risk model via multi-machine-learning algorithms for prognostic risk evaluation and clinical application in oral squamous cell carcinoma.Journal of translational medicine · 2025Article
- NLRX1 mediated impaired microglial phagocytosis of NETs in cerebral ischemia and reperfusion injury.Cell death and differentiation · 2025Article
- mTOR pathway targeted inhibition via Rapamycin-loaded PLGA nanoparticles for enhanced bladder cancer therapy.Scientific reports · 2025Article
- Heterologous prime-boost immunization of two-component vaccine candidate PWDVax protected pigs against F18 enterotoxigenicInfection and immunity · 2025Article
- Noncanonical feedback loop between "RIP3-MLKL" and "4EBP1-eIF4E" promotes neuronal necroptosis.MedComm · 2025Article
- Antileukemic effect of venetoclax and hypomethylating agents via caspase-3/GSDME-mediated pyroptosis.Journal of translational medicine · 2023Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex.iScience · 2022Article
- A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.Developmental cell · 2021Article
- The Role of mTOR Signaling as a Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Pim-1 Protects Retinal Ganglion Cells by Enhancing Their Regenerative Ability Following Optic Nerve Crush.Experimental neurobiology · 2020Article
- Targeted inhibition of mRNA translation initiation factors as a novel therapeutic strategy for mature B-cell neoplasms.Exploration of targeted anti-tumor therapy · 2020Article
- Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.Leukemia · 2020Article
- Review
- Targeting EZH1/2 induces cell cycle arrest and inhibits cell proliferation through reactivation of p57Cancer biology & medicine · 2019Article
- Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non-Hodgkin lymphoma.Cancer medicine · 2019Article
- 4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer.Cancer research · 2019Article
- 2'-Hydroxyflavanone induced changes in the proteomic profile of breast cancer cells.Journal of proteomics · 2019Article
- Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E/4E-BP axis.PLoS pathogens · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Mechanistic target of rapamycin (mTOR) complex 1 is a central integrator of nutrient and growth factor inputs that controls cell growth in eukaryotes. The second generation of mTOR kinase inhibitors (TORKi), directly targeting the mTOR catalytic site, are more effective than rapamycin and its analogs in cancer treatment, particularly in inducing apoptosis. However, the mechanism underlying the cytotoxic effect of TORKi remains elusive. Herein, we demonstrate that TORKi-induced apoptosis is predominantly dependent on the loss of mTOR complex 1-mediated 4EBP activation. Knocking out RICTOR, a key component of mTOR complex 2, or inhibiting p70S6K has little effect on TORKi-induced apoptosis. Conversely, increasing the eIF4E:4EBP ratio by either overexpressing eIF4E or knocking out 4EBP1/2 protects lymphoma cells from TORKi-induced cytotoxicity. Furthermore, downregulation of MCL1 expression plays an important role in TORKi-induced apoptosis, whereas BCL-2 overexpression confers resistance to TORKi treatment. We further show that the therapeutic effect of TORKi in aggressive B-cell lymphomas can be predicted by BH3 profiling, and improved by combining it with pro-apoptotic drugs, especially BCL-2 inhibitors, both
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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.