30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number14098
JournalNature Communications
Volume8
DOIs
StatePublished - Jan 19 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers'. Together they form a unique fingerprint.

  • Cite this