Abstract C151: Single and combined inhibition of AURKA and AURKB promotes a decrease in the expression of EMT biomarkers and transcription factors in triple-negative breast cancer in women of African ancestry

Abstract A major health disparity exists between Hispanic/Latino women (H/L) and women of African heritage (non-Hispanic black, NHB, Black H/L, and Caribbean H/L) compared to non-Hispanic White women (NHW) as they are more likely to die from breast cancer. Major contributors to these disparities are socioeconomic status, the detection of breast cancers at later stages, and higher rates of triple-negative breast cancer (TNBC). Molecularly, NHB women have increased expression of mRNAs coding for proteins that regulate the cell cycle, including the cyclins, centrosome, and mitotic kinases. TNBC lacks the estrogen receptor (ER), the progesterone receptor (PR), and the ERBB2 (HER2) receptor, which makes it even more challenging to treat with biological therapies. Mitotic kinases such as AURKA and AURKB are proteins essential for the cell cycle that promote normal cell division, the former involved in centrosome separation and the latter in regulating the spindle assembly checkpoint (SAC). However, when overexpressed, they can activate molecular pathways leading to the activation of centrosome amplification, chromosome instability, and early metastasis (epithelial-to-mesenchymal or EMT biomarkers, cell invasion, and migration) through transcription factors that could lead to a more aggressive breast cancer subtype, such as TNBC. This suggests that these mitotic kinases can drive cancer initiation and evolution. Hence, we hypothesize that co-inhibiting AURKA and AURKB will decrease the expression of EMT biomarkers and transcription factors and therefore, early metastasis. Using The Cancer Genome Atlas database, we identified higher expression of AURKA and AURKB in NHB women compared to NHW women and increased expression of AURKB in NHB women with TNBC. After 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 from the immunoblotting indicates that the expression of AURKA and AURKB decreased in all cell lines compared to the control group, and the EMT biomarker Vimentin decreased in MDA-MB-157 after targeting both mitotic kinases singly and in combination. At a genetic level, EMT biomarkers such as Vimentin, N- Cadherin, and transcription factors such as Slug, Twist, Snail, and Zeb1 decreased in the MDA- MB-157 cell line after single and combined inhibition. These results suggest the role of AURKA and AURKB in TNBC and their potential as therapeutic targets in TNBC. Eventually, we are going to be evaluating cell migration, invasion, tumor growth, and metastasis rates after co- inhibiting AURKA and AURKB in TNBC. Because of their more prevalent expression in breast cancers from NHB women, these kinases may represent new treatment modalities for women of African heritage. Citation Format: Joel A. Orengo-Orengo, Melanie Cruz, Alexandra Aquino, Harold I. Saavedra. Single and combined inhibition of AURKA and AURKB promotes a decrease in the expression of EMT biomarkers and transcription factors in triple-negative breast cancer in women of African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C151.