Abstract 4085: Depletion of Runx1 promotes epithelial to mesenchymal transition in breast cancer

Abstract

Abstract Runx1 is an essential transcription factor for definitive hematopoiesis and Runx1 translocations are well established as the causative factor of various leukemias. Recent studies have identified Runx1 as one of the most frequently mutated genes in breast cancer patients, and also that Runx1 expression levels are decreased in high-grade primary breast tumors compared to low/mid-grade tumors. The recognition of Runx1 expression in epithelial lining cells of glands suggests that Runx1 functions in maintaining the integrity of that cell layer. Therefore we examined the role of Runx1 during cancer progression. We found that Runx1 is highly expressed in immortalized human mammary epithelial cells (MCF10A) compared with breast cancer epithelial cells (MCF7) and invasive breast cancer cells (MDA-MB-231). To test the hypothesis that Runx1 contributes to the epithelial to mesenchymal transition (EMT) in breast cancer, the EMT was induced in MCF10A cells which resulted in a 50% decrease of Runx1 mRNA, but complete loss of Runx1 protein. This finding suggests a role for Runx1 as an EMT suppressor. To further address the relationship between Runx1 and EMT, Runx1 depleted stable cell lines were generated in both MCF10A and MCF7 cells. We observed that Runx1 knockdown (90%) in MCF10A cells leads to a dramatic change in their morphology towards a mesenchymal state, with a concomitant decrease in expression of the epithelial marker E-cadherin. In addition Runx1 depletion in MCF7 cells directly induced EMT state by repression of E-cadherin, as well as increased expression of mesenchymal genes, including vimentin, N-cadherin and fibronectin. Our results highlight a crucial role for Runx1 in preventing epithelial to mesenchymal transition and tumor progression in breast cancer. This Runx1 mediated mechanism points to novel intervention strategies for early stage breast cancer. Citation Format: Deli Hong, Jane Lian, Janet Stein, Gary Stein. Depletion of Runx1 promotes epithelial to mesenchymal transition in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4085. doi:10.1158/1538-7445.AM2015-4085