Abstract 4333: GCN5 positively correlates with c-MYC in non-small cell lung cancer

Lung cancer causes the highest mortality in cancer-related deaths. Definition of novel molecular targets is needed since these cancers often become resistant to existing therapies. Epigenetic modifications may provide such targets. Recent reports suggest that the histone acetyltransferase (HAT) module within the transcriptional coactivator SAGA complex plays a role in cancer, creating a new link between epigenetic regulators and this disease. We aim to define the role of the SAGA HAT protein GCN5 in the regulation and function of oncogenes in lung cancers. Since prior work indicates that GCN5 regulates the stability of c-MYC and serves as a coactivator for MYC target genes, we hypothesize that there is a positive relationship between GCN5 and c-MYC in non-small cell lung cancer (NSCLC). We also propose that inhibition of GCN5 will reduce lung cancer formation and progression in mouse models of lung cancer driven by c-MYC overexpression. Our data indicate that both GCN5 and c-MYC proteins are upregulated in NSCLC cells compared to normal lung epithelial cell lines. This trend is observable only at the protein level, indicating that the upregulation of these proteins in NSCLC cells occurs post-transcriptionally. Both GCN5 and c-MYC expression levels are also positively associated in mouse and human NSCLC cell lines. Genetic repression of GCN5 in NSCLC cells reduces cell proliferation, increases the population of necrotic cells, and reduces c-MYC expression. Inhibition of the GCN5 active site using commercially available probes in NSCLC cells significantly (p Citation Format: Lisa Maria Mustachio, Jason Roszik, Aimee Farria, Sharon YR Dent. GCN5 positively correlates with c-MYC in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4333.