Abstract PS2-13-05: Transcriptomic regulation by pregnane x receptor drives pro-migratory signaling in human breast cancer cells

Abstract The expression and activation of the nuclear receptor Pregnane X Receptor (PXR) has been linked with poor outcomes in human breast cancer. While PXR's canonical role in drug metabolism is well defined in the liver and gastrointestinal tract, its contribution to tumor progression is less understood. We sought to define transcriptomic regulation mediated by PXR in breast cancer cells and its potential impact on metastasis. Triple-negative MDA-MB-231 cells were engineered to stably overexpress human PXR and treated with the agonist rifampicin. RNA-seq analysis revealed significant transcriptional changes compared with controls. KEGG and Gene Ontology enrichment identified pathways associated with cytoskeleton remodeling, adhesion complex components, and motility regulators. A panel of ten genes previously implicated in cancer cell migration was consistently up regulated (log2FC > 1.7; p <0.05). Post-hoc qPCR validation confirmed these results. Collectively, these data indicate that PXR expression enhances pro-migratory transcriptional pathways in breast tumor cells, providing mechanistic insight into its potential role as a driver of breast cancer metastasis and contributor to poor prognosis. Citation Format: C. E. Elliott, D. Brobst, V. Nguyen, C. Ballard, A. Youssef, W. Dye, R. M. Bodily, A. Ko, J. L. Staudinger, B. A. Creamer. Transcriptomic regulation by pregnane x receptor drives pro-migratory signaling in human breast cancer cells [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-05.