Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.
Authors | |
Abstract | Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers. |
Year of Publication | 2018
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Journal | Nat Commun
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Volume | 9
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Issue | 1
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Pages | 5450
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Date Published | 2018 Dec 21
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ISSN | 2041-1723
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DOI | 10.1038/s41467-018-07824-4
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PubMed ID | 30575730
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PubMed Central ID | PMC6303303
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Grant list | T32 CA009172 / CA / NCI NIH HHS / United States
P01 CA154303 / CA / NCI NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States
F32 CA196141 / CA / NCI NIH HHS / United States
R35 CA197568 / CA / NCI NIH HHS / United States
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