Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Gannon, HS, Zou, T, Kiessling, MK, Gao, GF, Cai, D, Choi, PS, Ivan, AP, Buchumenski, I, Berger, AC, Goldstein, JT, Cherniack, AD, Vazquez, F, Tsherniak, A, Levanon, EY, Hahn, WC, Meyerson, M |
Journal | Nat Commun |
Volume | 9 |
Issue | 1 |
Pages | 5450 |
Date Published | 2018 Dec 21 |
ISSN | 2041-1723 |
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. |
DOI | 10.1038/s41467-018-07824-4 |
Pubmed | |
Alternate Journal | Nat Commun |
PubMed ID | 30575730 |
PubMed Central ID | PMC6303303 |
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 |