Abstract 1389: Insights into the invasiveness of triple-negative breast cancer from genome-wide profiling of AP-1

Triple-negative breast cancer (TNBC) is an aggressive clinical phenotype, and accounts for 15% to 20% of all breast cancers. The molecular determinants of malignant cell behaviors in TNBC remain largely unknown. We show that the AP-1 transcription factor component Fra-1 is overexpressed in basal-like breast tumors, often referred to as TNBCs, and that its expression level has high prognostic significance. Depletion of Fra-1 or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Furthermore, knockdown of Fra-1 or c-Jun also reduces cellular invasion in vivo in a zebrafish xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we provide insights into the transcriptional regulatory networks of AP-1 in TNBC cells. We identify direct targets of the Fra-1/c-Jun heterodimer involved in cell proliferation, cell adhesion, and cell-cell contact. Importantly, we show that AP-1 represses E-cadherin expression by transcriptional upregulation of ZEB2, thereby stimulating cell invasion. This work sheds light on mechanisms and pathways by which TNBCs acquire invasiveness and proliferative propensity. Note: This abstract was not presented at the meeting. Citation Format: Chunyan Zhao, Yichun Qiao, Karin Dahlman-Wright. Insights into the invasiveness of triple-negative breast cancer from genome-wide profiling of AP-1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1389. doi:10.1158/1538-7445.AM2014-1389