ArticleThe Journal of clinical investigation2017
MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR.Cell death and differentiation · 2026Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis.Science advances · 2024Article
- Molecular Analysis of Murine KitJID innovations : skin science from molecules to population health · 2024Article
- MiR-125b targeted regulation of MKNK2 inhibits multiple myeloma proliferation and invasion.American journal of translational research · 2024Article
- Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.PLoS biology · 2023Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- An Aptamer against MNK1 for Non-Small Cell Lung Cancer Treatment.Pharmaceutics · 2023Article
- MNK Proteins as Therapeutic Targets in Leukemia.OncoTargets and therapy · 2023Review
- Identification ofComputational and structural biotechnology journal · 2023Article
- Design, Synthesis and Evaluation of Novel Phorbazole C Derivatives as MNK Inhibitors through Virtual High-Throughput Screening.Marine drugs · 2022Article
- Inhibition of MNKs promotes macrophage immunosuppressive phenotype to limit CD8+ T cell antitumor immunity.JCI insight · 2022Article
- Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor.Journal of medicinal chemistry · 2022Article
- The role of immune checkpoints in cardiovascular disease.Frontiers in pharmacology · 2022Review
- Potential therapies for immune-related adverse events associated with immune checkpoint inhibition: from monoclonal antibodies to kinase inhibition.Journal for immunotherapy of cancer · 2022Review
- Sorafenib treatment of metastatic melanoma with c-Kit aberration reduces tumor growth and promotes survival.Oncology letters · 2021Article
- The functional GRHL3-filaggrin axis maintains a tumor differentiation potential and influences drug sensitivity.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Immunotherapies targeting stimulatory pathways and beyond.Journal of hematology & oncology · 2021Review
- MNK Inhibition SensitizesCancer discovery · 2021Article
- Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates antitumor immune responses.The Journal of clinical investigation · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and reduced metastatic ability. Clinically, tumors from melanoma patients harboring KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations.
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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.