You are here

Nat Commun DOI:10.1038/s41467-018-07824-4

Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.

Publication TypeJournal Article
Year of Publication2018
AuthorsGannon, 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
JournalNat Commun
Volume9
Issue1
Pages5450
Date Published2018 Dec 21
ISSN2041-1723
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.

DOI10.1038/s41467-018-07824-4
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/30575730?dopt=Abstract

Alternate JournalNat Commun
PubMed ID30575730
PubMed Central IDPMC6303303
Grant ListT32 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