Abstract 5138: NRAS overexpression influences EMT in claudin-low triple negative breast cancer

Abstract This study investigates Nras-mediated Ras-Mapk in epithelial-mesenchymal transition and the therapeutic potential of RAS-MAPK inhibitors in Claudin-low(CL) triple-negative breast cancer (TNBC). The K14TRT line represents a potential model for CL and metastatic TNBC research due to its genomic similarities to human CL, TNBC. Research at the Perou Lab indicated that the K14TRT cell line exhibited great expression of the NRAS gene, which may influence the EMT characteristics of the cell line. NRAS influences EMT by altering the expression of signaling proteins involving stem-cell characteristics, cell-to-cell attachment, and cell growth regulators. Subsequent knockout of NRAS via siRNA transfection and use of the MEK inhibitor Trametinib were used to observe changes in transcriptome expression. These changes in the transcriptome will then be analyzed to identify future vulnerabilities in the K14TRT cell line using significance analysis of microarray (SAM) in R-Studio. TNBC lacks targeted treatments that other subtypes of breast cancer have, leading to significant disparities in the 5-year survival rate of breast cancer (78.0% for TNBC vs. 91.2% AVG). In addition, triple-negative breast cancer disproportionately affects young Black American and pre-menopausal women. This study highlights the potential influence of NRAS-mediated RAS-MAPK on EMT in Claudin-low, TNBC. Highlighting the RAS-MAPK pathway for its potential use as a primary target in CL, TNBC. Citation Format: Jackson Marlon Rodney Thomas, Stephanie Dance-Barnes. NRAS overexpression influences EMT in claudin-low triple negative breast cancer [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 5138.