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Excel · study · 2026

Cytoplasmic ATM restricts oncolytic VSVΔ51 replication by sustaining TBK1-IRF3 signaling in glioblastoma cells

Listed in NCBI GEO

ATM is a nuclear DNA damage response kinase with tumor-suppressive functions, but its cytoplasmic function during virus infection remains poorly understood.

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Here, we identify cytoplasmic ATM as an antiviral factor that restricts oncolytic virus (OVs) replication. Infection with oncolytic VSVΔ51 triggered CRM1-dependent nuclear export of ATM, generating cytoplasmic ATM that associated with viral dsRNA-containing complexes.

Blocking ATM nuclear export or inhibiting ATM attenuated type I interferon induction, thereby licensing viral replication. Mechanistically, cytoplasmic ATM interacted with the ubiquitin-like domain of TBK1 and sustained TBK1-IRF3 signaling. ATM inhibition potentiated oncolytic cytotoxicity and promoted immunogenic cell death in cancer cells.

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In multiple tumor models, pharmacological inhibition or genetic loss of ATM cooperated with VSVΔ51 to suppress tumor growth, prolong survival of mice, and promote durable antitumor immunity. These findings reveal the cytoplasmic function of ATM in antiviral innate immunity and identify it as a therapeutic vulnerability for improving oncolytic virotherapy.

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Life Sciences
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Cancer 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34207215 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title