ArticleMolecular cancer research : MCR2016
MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Aptamer-based inhibition of MNK1 reduces pancreatic ductal adenocarcinoma growth by targeting cancer stem cells.Journal of biomedical science · 2026Article
- Article
- Development of a Direct-to-Biology Platform to Discover Potent MNK Inhibitors.Journal of medicinal chemistry · 2026Article
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis.Science advances · 2024Article
- miR-483-5p orchestrates the initiation of protein synthesis by facilitating the decrease in phosphorylated Ser209eIF4E and 4E-BP1 levels.Scientific reports · 2024Article
- A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.Journal of cellular and molecular medicine · 2023Article
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.Molecular therapy. Nucleic acids · 2022Article
- Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide.Scientific reports · 2022Article
- MNK Inhibition SensitizesCancer discovery · 2021Article
- Article
- Phosphorylation of the mRNA cap-binding protein eIF4E and cancer.Cellular signalling · 2020Review
- Article
- Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020Review
- Insights Into Translatomics in the Nervous System.Frontiers in genetics · 2020Review
- Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential.Cells · 2019Review
- AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.Molecular cancer · 2019Review
- Pharmacological mTOR targeting enhances the antineoplastic effects of selective PI3Kα inhibition in medulloblastoma.Scientific reports · 2019Article
- First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer.The oncologist · 2019Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Glioblastoma multiforme remains the deadliest malignant brain tumor, with glioma stem cells (GSC) contributing to treatment resistance and tumor recurrence. We have identified MAPK-interacting kinases (MNK) as potential targets for the GSC population in glioblastoma multiforme. Isoform-level subtyping using The Cancer Genome Atlas revealed that both MNK genes (MKNK1 and MKNK2) are upregulated in mesenchymal glioblastoma multiforme as compared with other subtypes. Expression of MKNK1 is associated with increased glioma grade and correlated with the mesenchymal GSC marker, CD44, and coexpression of MKNK1 and CD44 predicts poor survival in glioblastoma multiforme. In established and patient-derived cell lines, pharmacologic MNK inhibition using LY2801653 (merestinib) inhibited phosphorylation of the eukaryotic translation initiation factor 4E, a crucial effector for MNK-induced mRNA translation in cancer cells and a marker of transformation. Importantly, merestinib inhibited growth of GSCs grown as neurospheres as determined by extreme limiting dilution analysis. When the effects of merestinib were assessed in vivo using an intracranial xenograft mouse model, improved overall survival was observed in merestinib-treated mice. Taken together, these data provide strong preclinical evidence that pharmacologic MNK inhibition targets mesenchymal glioblastoma multiforme and its GSC population. IMPLICATIONS: These findings raise the possibility of MNK inhibition as a viable therapeutic approach to target the mesenchymal subtype of glioblastoma multiforme. Mol Cancer Res; 14(10); 984-93. ©2016 AACR.
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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.