Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer.

Autor: Kung CP; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Cottrell KA; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Ryu S; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Bramel ER; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Kladney RD; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Bao EA; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Freeman EC; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Sabloak T; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Maggi L Jr; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA., Weber JD; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, MO, USA. jweber@wustl.edu.; Department of Cell Biology and Physiology, Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO, USA. jweber@wustl.edu.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2021 Jan; Vol. 40 (1), pp. 189-202. Date of Electronic Publication: 2020 Oct 27.
DOI: 10.1038/s41388-020-01515-5
Abstrakt: Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of endogenous double-stranded RNAs. ADAR1 is highly expressed in breast cancer including TNBC. Here, we demonstrate that expression of ADAR1, specifically its p150 isoform, is required for the survival of TNBC cell lines. In TNBC cells, knockdown of ADAR1 attenuates proliferation and tumorigenesis. Moreover, ADAR1 knockdown leads to robust translational repression. ADAR1-dependent TNBC cell lines also exhibit elevated IFN stimulated gene expression. IFNAR1 reduction significantly rescued the proliferative defects of ADAR1 loss. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.
Databáze: MEDLINE
Externí odkaz: