Abstract PO-147: Targeting Notch signaling in cancer stem-like cells of triple-negative breast cancer

Abstract

Abstract Triple-Negative Breast Cancer (TNBC) is an aggressive form of breast cancer. This particular type expresses no Estrogen (ER) and Progesterone (PR) hormone receptors or Human epidermal growth factor receptor-2 amplifications. African American women are more frequently affected at a younger age by this aggressive breast cancer than any other ethnicity. Furthermore, heterogeneity of cells within a tumor challenges to identify specific targets to develop new drugs. Specifically, a subpopulation of cells within a tumor, called cancer stem-like cells (CSC) are known to grow slower, resist treatments, and be responsible for the relapse and metastasis of a tumor. Notch signaling pathway, which is one of the key regulatory signaling pathways in normal and cancer stem cells. We hypothesize that Notch1 signaling is a crucial signaling pathway for TNBC and worthwhile to target. To be able to identify and test Notch-specific targeted drugs, it is crucial to establish a cell line that overexpresses and knocks down the target gene. Therefore, in this project, we establish Notch1 modified stable TNBC cell lines and checked their morphological and physiological changes. Using MDA-MB-231 TNBC cell line, for the Notch1 knockout, we used crisper/cas9 gene-editing method and clonal selection of knockout cells. For the overexpression of NOTCH1 intracellular domain, we constructed and used pBABE-puro lentivirus system. Our results showed the Notch1 KO cells become more epithelial-like in appearance, with reduced expression of CD44+/CD24lo CSC markers, and reduced capacity to form mammospheres. On the other hand, overexpression of Notch1 the CSC become more mesenchymal and increase the expression of CSC markers. Also, we observed reduced metabolic activity of our Notch1KO cells while the overexpression of Notch1 increased the metabolic activity of the TNBC cells. Our preliminary results show that targeting Notch signaling is a promising approach to cure TNBC patients suffering from this aggressive cancer. Citation Format: Adrienne M. Murphy, Ayse D. Ucar, Lucio Miele. Targeting Notch signaling in cancer stem-like cells of triple-negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-147.