ArticlePloS one2012
Suppression of IFN-induced transcription underlies IFN defects generated by activated Ras/MEK in human cancer cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 43 citations in OpenAlex.
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- Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comprehensive Analysis of Tumor Microenvironment Reveals Prognostic ceRNA Network Related to Immune Infiltration in Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Intertumoral heterogeneity impacts oncolytic vesicular stomatitis virus efficacy in mouse pancreatic cancer cells.Journal of virology · 2023Article
- Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection.Frontiers in immunology · 2023Article
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- RegEnrich gene regulator enrichment analysis reveals a key role of the ETS transcription factor family in interferon signaling.Communications biology · 2022Article
- Deletion of immunomodulatory genes as a novel approach to oncolytic vaccinia virus development.Molecular therapy oncolytics · 2021Article
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- The Regulatory Role of Reticulons in Neurodegeneration: Insights Underpinning Therapeutic Potential for Neurodegenerative Diseases.Cellular and molecular neurobiology · 2021Review
- Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?Frontiers in oncology · 2021Review
- Past, Present and Future of Oncolytic Reovirus.Cancers · 2020Review
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- MEK1/2 Inhibitors Unlock the Constrained Interferon Response in Macrophages Through IRF1 Signaling.Frontiers in immunology · 2019Article
- Unscheduled HDAC4 repressive activity in human fibroblasts triggers TP53-dependent senescence and favors cell transformation.Molecular oncology · 2018Article
- Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses.Reviews in medical virology · 2018Review
- The MEK1/2-ERK Pathway Inhibits Type I IFN Production in Plasmacytoid Dendritic Cells.Frontiers in immunology · 2018Article
- Up-regulation of GBP2 is Associated with Neuronal Apoptosis in Rat Brain Cortex Following Traumatic Brain Injury.Neurochemical research · 2017Article
- A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Certain oncolytic viruses exploit activated Ras signaling in order to replicate in cancer cells. Constitutive activation of the Ras/MEK pathway is known to suppress the effectiveness of the interferon (IFN) antiviral response, which may contribute to Ras-dependent viral oncolysis. Here, we identified 10 human cancer cell lines (out of 16) with increased sensitivity to the anti-viral effects of IFN-α after treatment with the MEK inhibitor U0126, suggesting that the Ras/MEK pathway underlies their reduced sensitivity to IFN. To determine how Ras/MEK suppresses the IFN response in these cells, we used DNA microarrays to compare IFN-induced transcription in IFN-sensitive SKOV3 cells, moderately resistant HT1080 cells, and HT1080 cells treated with U0126. We found that 267 genes were induced by IFN in SKOV3 cells, while only 98 genes were induced in HT1080 cells at the same time point. Furthermore, the expression of a distinct subset of IFN inducible genes, that included RIGI, GBP2, IFIT2, BTN3A3, MAP2, MMP7 and STAT2, was restored or increased in HT1080 cells when the cells were co-treated with U0126 and IFN. Bioinformatic analysis of the biological processes represented by these genes revealed increased representation of genes involved in the anti-viral response, regulation of apoptosis, cell differentiation and metabolism. Furthermore, introduction of constitutively active Ras into IFN sensitive SKOV3 cells reduced their IFN sensitivity and ability to activate IFN-induced transcription. This work demonstrates for the first time that activated Ras/MEK in human cancer cells induces downregulation of a specific subset of IFN-inducible genes.
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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.