Nature communications, 2017-01, Vol.8 (1), p.14098-14098, Article 14098
2017
Details
- Autor(en) / Beteiligte
- Titel
- SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers
- Ist Teil von
- Nature communications, 2017-01, Vol.8 (1), p.14098-14098, Article 14098
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells. AURKA inhibitors may provide a therapeutic strategy for biomarker-driven clinical studies to treat the NSCLCs harbouring SMARCA4/BRG1-inactivating mutations.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms14098Titel-ID: cdi_doaj_primary_oai_doaj_org_article_f81ec3448b26422b8d9847f84e7abb5c
- Format
- –
- Schlagworte
- Animals, Apoptosis, Aurora Kinase A - antagonists & inhibitors, Aurora Kinase A - metabolism, Carcinoma, Non-Small-Cell Lung - drug therapy, Carcinoma, Non-Small-Cell Lung - genetics, Cell Line, Tumor, Cell Survival, Cells, DNA Helicases - genetics, DNA Helicases - metabolism, Female, Gene Expression Regulation, Neoplastic, Genes, Genome-Wide Association Study, Genomes, Genomics, High-Throughput Nucleotide Sequencing, Humans, Kinases, Lung cancer, Lung Neoplasms - drug therapy, Lung Neoplasms - genetics, Mice, Mice, SCID, Mutation, Neoplasms, Experimental, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Oncology, Piperazines - pharmacology, Protein Kinase Inhibitors - pharmacology, Proteins, RNA Interference, RNA, Small Interfering, Transcription Factors - genetics, Transcription Factors - metabolism, Tumors