Abstract 6958: Combined targeting of AURKA and AURKB as a potential therapeutic strategy to decrease the expression of epithelial-to-mesenchymal transition drivers in triple-negative breast cancers

Abstract Studies have shown a significant health disparity between Hispanic/Latino women (H/L) and women of African ancestry (non-Hispanic black (NHB), Black H/L, and Caribbean H/L) compared to non-Hispanic White women (NHW) as they are more likely to be diagnosed with and to die from triple-negative breast cancer (TNBC). At mRNA levels, NHB women diagnosed with TNBC overexpress mitotic kinases such as AURKA and AURKB relative to NHW. Although these mitotic kinases have a pivotal role in the cell cycle, when dysregulated, they can activate epithelial-to-mesenchymal transition (EMT) drivers that can lead to metastasis and therapy resistance. TNBC is the most aggressive breast cancer subtype that lacks the progesterone (PR), estrogen (ER), and the ERBB2 (HER2) receptor. Therefore, it cannot be treated with biological therapies that are known to be effective against the other molecular subtypes. Thus, the purpose of this study is to investigate if AURKA and AURKB are potential therapeutic targets against TNBC in women of African ancestry. Hence, we hypothesize that co-inhibiting AURKA and AURKB will decrease the expression of EMT biomarkers and transcription factors and, therefore, lead to early metastasis. Using The Cancer Genome Atlas Database (TCGA), we identified higher expression of AURKA and AURKB in NHB women than in NHW women and increased expression of AURKB in NHB women with TNBC. After 4-siRNA-mediated knockdown, immunoblotting and Real-Time qPCR were performed using the MDA-MB-231 cells (NHW) and MDA-MB-157 (NHB) mesenchymal TNBC cells. Preliminary data indicates that the expression of AURKA and AURKB decreased in all cell lines compared to the control group. N-cadherin protein level decreased in MDA-MB-231 after a single inhibition, while the levels of ZO-1 increased after combined inhibition. Vimentin decreased in MDA-MB-157 after AURKB inhibition, while the levels of Snail decreased after combined inhibition. At mRNA levels, AURKA and AURKB significantly reduced in both cell lines and levels of Twist decreased in MDA-MB-231 after co-inhibiting AURKA and AURKB. Preliminary data from invasion assays suggest a decrease in invasion ability after single and combined inhibition in both cell lines. We will perform a prolonged transfection using shRNA to evaluate the expression of these EMT biomarkers. Additionally, we will study tumor growth and metastasis rates in vivo models. In conclusion, these results suggest the role of AURKA and AURKB in TNBC and their potential as therapeutic targets to decrease early metastasis. Citation Format: Joel Alexis Orengo, William Frank Rodríguez, Selimar Álvarez Velázquez, Alexandra N. Aquino- Acevedo, Gabriel Rosario Ortíz, Melanie E. Cruz Robles, Esther M. Irrizary Quintana, Harold I. Saavedra. Combined targeting of AURKA and AURKB as a potential therapeutic strategy to decrease the expression of epithelial-to-mesenchymal transition drivers in triple-negative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6958.