Ontology highlight
ABSTRACT:
SUBMITTER: Chiappinelli KB
PROVIDER: S-EPMC4556003 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
Chiappinelli Katherine B KB Strissel Pamela L PL Desrichard Alexis A Li Huili H Henke Christine C Akman Benjamin B Hein Alexander A Rote Neal S NS Cope Leslie M LM Snyder Alexandra A Makarov Vladimir V Budhu Sadna S Slamon Dennis J DJ Wolchok Jedd D JD Pardoll Drew M DM Beckmann Matthias W MW Zahnow Cynthia A CA Merghoub Taha T Chan Timothy A TA Baylin Stephen B SB Strick Reiner R
Cell 20150801 5
We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a type I interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response 2-fold and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV ove ...[more]