ArticleOncotarget2014
Regulatory effects of a Mnk2-eIF4E feedback loop during mTORC1 targeting of human medulloblastoma cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.International journal of molecular sciences · 2021Pooled it
- Review
- Development of a SIN1 Targeting Inhibitor as a Novel Therapeutic Approach for the Treatment of Malignancies.Molecular cancer therapeutics · 2026Article
- Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome.Molecular psychiatry · 2026Article
- Exploring the Molecular Complexity of Medulloblastoma: Implications for Diagnosis and Treatment.Diagnostics (Basel, Switzerland) · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy.Current treatment options in oncology · 2021Review
- Inhibitory effects of Tomivosertib in acute myeloid leukemia.Oncotarget · 2021Article
- Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.Cellular and molecular life sciences : CMLS · 2021Article
- Combined PI3Kα-mTOR Targeting of Glioma Stem Cells.Scientific reports · 2020Article
- The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma.International journal of molecular sciences · 2020Review
- Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020Review
- Inhibitory effects of SEL201 in acute myeloid leukemia.Oncotarget · 2019Article
- Article
- Pharmacological mTOR targeting enhances the antineoplastic effects of selective PI3Kα inhibition in medulloblastoma.Scientific reports · 2019Article
- Potent Antineoplastic Effects of Combined PI3Kα-MNK Inhibition in Medulloblastoma.Molecular cancer research : MCR · 2019Article
- The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis.Cancers · 2019Article
- MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells.Acta pharmacologica Sinica · 2018Article
- eIF4E Phosphorylation in Prostate Cancer.Neoplasia (New York, N.Y.) · 2018Review
- Improved therapy for medulloblastoma: targeting hedgehog and PI3K-mTOR signaling pathways in combination with chemotherapy.Oncotarget · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
The mTOR pathway controls mRNA translation of mitogenic proteins and is a central regulator of metabolism in malignant cells. Development of malignant cell resistance is a limiting factor to the effects of mTOR inhibitors, but the mechanisms accounting for such resistance are not well understood. We provide evidence that mTORC1 inhibition by rapamycin results in engagement of a negative feedback regulatory loop in malignant medulloblastoma cells, involving phosphorylation of the eukaryotic translation-initiation factor eIF4E. This eIF4E phosphorylation is Mnk2- mediated, but Mnk1-independent, and acts as a survival mechanism for medulloblastoma cells. Pharmacological targeting of Mnk1/2 or siRNA-mediated knockdown of Mnk2 sensitizes medulloblastoma cells to mTOR inhibition and promotes suppression of malignant cell proliferation and anchorage-independent growth. Altogether, these findings provide evidence for the existence of a Mnk2-controlled feedback loop in medulloblastoma cells that accounts for resistance to mTOR inhibitors, and raise the potential for combination treatments of mTOR and Mnk inhibitors for the treatment of medulloblastoma.
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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.