ArticleInternational journal of molecular sciences2017
The MEK Inhibitors Trametinib and Cobimetinib Induce a Type I Interferon Response in Human Keratinocytes.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy.Nature communications · 2025Article
- Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models.Molecular cancer therapeutics · 2024Article
- Predicting Survival Signature of Bladder Cancer Related to Cancer-Associated Fibroblast (CAF) Constructed by Intersecting Genes in TCGA and GEO.Molecular biotechnology · 2024Article
- Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.The Journal of investigative dermatology · 2024Article
- Strategies to overcome low MHC-I expression in paediatric and adult tumours.Immunotherapy advances · 2024Review
- A Critical Role for IFN-β Signaling for IFN-κ Induction in Keratinocytes.Frontiers in lupus · 2024Article
- Downregulation of PD-L1 and HLA-I in non-small cell lung cancer with ALK fusion.Thoracic cancer · 2022Article
- Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response.Frontiers in immunology · 2022Review
- VEGA is an interpretable generative model for inferring biological network activity in single-cell transcriptomics.Nature communications · 2021Article
- Interferon-inducer antivirals: Potential candidates to combat COVID-19.International immunopharmacology · 2021Review
- Targeted Mitochondrial Therapy With Over-Expressed MAVS Protein From Mesenchymal Stem Cells: A New Therapeutic Approach for COVID-19.Frontiers in cell and developmental biology · 2021Article
- Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation.Frontiers in immunology · 2021Review
- Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study.Frontiers in oncology · 2021Article
- Tyrosine Kinase Inhibitors Stimulate HLA Class I Expression by Augmenting the IFNγ/STAT1 Signaling in Hepatocellular Carcinoma Cells.Frontiers in oncology · 2021Article
- Antagonism of interferon signaling by fibroblast growth factors promotes viral replication.EMBO molecular medicine · 2020Article
- Multiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action.Nature communications · 2020Article
- The influence of interferon on healthy and diseased skin.Cytokine · 2020Review
- MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy.Cancers · 2020Review
- Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance.Journal of virology · 2020Article
- Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas.G3 (Bethesda, Md.) · 2019Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen-activated protein kinase kinases (MEK) 1 and 2 have crucial roles in tumorigenesis, cell proliferation, and protection from apoptosis, and their inhibition is therefore an attractive therapeutic strategy in cancer. Orally available and highly selective MEK inhibitors have been developed and assessed in numerous clinical trials, either alone or in combination with cytotoxic chemotherapy and/or other targeted agents. Of note, a complex picture of class-specific adverse effects associates with these drugs, frequently including inflammatory skin rash. Here, we investigated the response of normal human keratinocytes to the MEK inhibitors trametinib and cobimetinib, alone and in combination with the v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors dabrafenib and vemurafenib, in terms of signal transduction and de novo gene expression. MEK inhibitors triggered enhanced expression of interferon regulatory factor 1 (IRF1) and phosphorylation of signal transducer and activator of transcription 1 (STAT1), and up-regulated the keratinocyte-specific type I interferon κ (IFN-κ), the anti-viral effectors interferon-induced tetratricopeptide repeats (IFIT) 1 and 2, and the pro-inflammatory chemokine (C-C motif) ligand 2 (CCL2) and the C-X-C motif chemokine 10 (CXCL10), both at the mRNA and protein level. Impairment of IRF1 expression, or abrogation of STAT1 phosphorylation due to
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